Before configuring your app to enable use of 65K or more method references, you should take steps to reduce the total number of references called by your app code, including methods defined by your app code or included libraries. The following strategies can help you avoid hitting the dex reference limit:
Review your app's direct and transitive dependencies - Ensure any large library dependency you include in your app is used in a manner that outweighs the amount of code being added to the application. A common anti-pattern is to include a very large library because a few utility methods were useful. Reducing your app code dependencies can often help you avoid the dex reference limit.
Remove unused code with ProGuard - Configure the ProGuard settings for your app to run ProGuard and ensure you have shrinking enabled for release builds. Enabling shrinking ensures you are not shipping unused code with your APKs.
Using these techniques can help you avoid the build configuration changes required to enable more method references in your app. These steps can also decrease the size of your APKs, which is particularly important for markets where bandwidth costs are high.