思路

com.alibaba.druid.pool.DruidAbstractDataSource.createPhysicalConnection
方法中，通过userCallback和passwordCallback可以对用户名密码进行自定义操作，内容如下

public PhysicalConnectionInfo createPhysicalConnection() throws SQLException {
  ***
        String user;
        if (getUserCallback() != null) {
            user = getUserCallback().getName();
        } else {
            user = getUsername();
        }

        String password = getPassword();
        PasswordCallback passwordCallback = getPasswordCallback();

        if (passwordCallback != null) {
            if (passwordCallback instanceof DruidPasswordCallback) {
                DruidPasswordCallback druidPasswordCallback = (DruidPasswordCallback) passwordCallback;

                druidPasswordCallback.setUrl(url);
                druidPasswordCallback.setProperties(connectProperties);
            }

            char[] chars = passwordCallback.getPassword();
            if (chars != null) {
                password = new String(chars);
            }
        }
  ***
}

userCallback和passwordCallback分别为

import javax.security.auth.callback.NameCallback;
import javax.security.auth.callback.PasswordCallback;

protected volatile PasswordCallback                passwordCallback;
protected volatile NameCallback                    userCallback;

public PasswordCallback getPasswordCallback() {
    return passwordCallback;
}

public void setPasswordCallback(PasswordCallback passwordCallback) {
    this.passwordCallback = passwordCallback;
}

public void setPasswordCallbackClassName(String passwordCallbackClassName) throws Exception {
    Class<?> clazz = Utils.loadClass(passwordCallbackClassName);
    if (clazz != null) {
        this.passwordCallback = (PasswordCallback) clazz.newInstance();
    } else {
        LOG.error("load passwordCallback error : " + passwordCallbackClassName);
        this.passwordCallback = null;
    }
}

public NameCallback getUserCallback() {
    return userCallback;
}

public void setUserCallback(NameCallback userCallback) {
    this.userCallback = userCallback;
}

直接引用druid情况

如果是直接引用druid而非autoconfig形式（即非druid-spring-boot-starter形式引入）
可以直接继承
om.alibaba.druid.pool.DruidDataSource
直接重写两个对两个callback进行赋值即可
spring.datasource.type=你自己实现的类

xml配置的情况

可以配置

<bean id="dataSource" class="com.alibaba.druid.pool.DruidDataSource" init-method="init" destroy-method="close">
        ***
         <property name="userCallback" ref="dbUserCallback"/>
         <property name="passwordCallback" ref="dbPasswordCallback"/>
        ***
</bean>

本文重点：application.yml的情况

因为yml无法引用bean或对象(本人没有找到对应方法，如果有大神知道，请告知)，且autoconfig是通过druiddatasourcewrapper来注入参数的。并且druid只提供了passwordCallback的className setter方法，因此只能做到对password的自定义加密解密，配置方法如下：

datasource:
    type: com.alibaba.druid.pool.DruidDataSource
    druid:
      passwordCallbackClassName: 你自定义的类全限定名

想要同时加密用户名密码就要用到filter代码入下：
application.yml

spring:
  datasource:
    type: com.alibaba.druid.pool.DruidDataSource
    druid:
      # 略过
      publicKey: aabbccdd
      db1: #数据源1
        driverClassName: com.mysql.cj.jdbc.Driver
        url: jdbc:mysql://127.0.0.1:3306/1
        username: admin
        password: admin
        connection-properties: publicKey=${spring.datasource.druid.publicKey};username=${spring.datasource.druid.db1.username};password=${spring.datasource.druid.db1.password}
      db2: #数据源2 
        driverClassName: com.mysql.cj.jdbc.Driver
        url: jdbc:mysql://127.0.0.1:3306/2
        username: admin
        password: admin
        connection-properties: publicKey=${spring.datasource.druid.publicKey};username=${spring.datasource.druid.db2.username};password=${spring.datasource.druid.db2.password}
      db3: #数据源3
        driverClassName: com.mysql.cj.jdbc.Driver
        url: jdbc:mysql://127.0.0.1:3306/3
        username: admin
        password: admin
        connection-properties: publicKey=${spring.datasource.druid.publicKey};username=${spring.datasource.druid.db3.username};password=${spring.datasource.druid.db3.password}
      db4: #数据源4 数栈的tidb库，统计指标用
        driverClassName: com.mysql.cj.jdbc.Driver
        url: jdbc:mysql://127.0.0.1:3306/4
        username: admin
        password: admin
        connection-properties: publicKey=${spring.datasource.druid.publicKey};username=${spring.datasource.druid.db4.username};password=${spring.datasource.druid.db4.password}

filter

import com.alibaba.druid.filter.FilterEventAdapter;
@Component
public class DataSourceFilter extends FilterEventAdapter {

    @Override
    public void init(DataSourceProxy dataSourceProxy) {
        DruidDataSource dataSource = (DruidDataSource) dataSourceProxy;
        dataSource.setUserCallback(new MyDruidUsernameCallback(dataSource.getConnectProperties()));
        dataSource.setPasswordCallback(new MyDruidPasswordCallback());
        super.init(dataSource);
    }
}

MyDruidPasswordCallback

import com.alibaba.druid.util.DruidPasswordCallback;
public class MyDruidPasswordCallback extends DruidPasswordCallback {
    @Override
    public void setProperties(Properties properties) {
        super.setProperties(properties);
        //获取application.yml 里面配置的密码和公钥
        String password = (String) properties.get("password");
        String publicKey = (String) properties.get("publicKey");
        if (password == null) return;
        try {
            // SMHelper 为自己的解密工具
            String decryptPassword = SMHelper.sm4Decrypt(publicKey, password);
            setPassword(decryptPassword.toCharArray());
        } catch (Exception e) {
            log.error("Druid ConfigTools.decrypt", e);
        }
    }
}

MyDruidUsernameCallback

import javax.security.auth.callback.NameCallback;
public class MyDruidUsernameCallback extends NameCallback {

    private final Properties properties;

    public MyDruidUsernameCallback(Properties properties) {
        super("no uses, i write aimlessly");
        this.properties = properties;
    }

    @Override
    public String getName() {
        String username = (String) properties.get("username");
        String publicKey = (String) properties.get("publicKey");

        try {
            // SMHelper 为自己的解密工具
            String decryptUserName = SMHelper.sm4Decrypt(publicKey, username);
            super.setName(decryptUserName);
        } catch (Exception e) {
            log.error("Druid ConfigTools.decrypt", e);
        }
        return super.getName();
    }
}

备注

如果可以修改druid源码的话，github上有老哥给出了其他解决方案：
支持自定义password-callback & add test case by JoeyBling · Pull Request #3877 · alibaba/druid · GitHub