Literally, “matters of indifference.” Beliefs or practices which the sixteenth-century Reformers regarded as being tolerable, in that they were neither explicitly rejected nor stipulated by Scripture. For example, what ministers wore at church services was often regarded as a “matter of indifference.” The concept is of importance in that it allowed the sixteenth-century reformers to adopt a pragmatic approach to many beliefs and practices, thus avoiding unnecessary confrontation.

TheoGlossary, originated from Biblicist.org

What does this mean in light of things like the “regulative principle”?

We stick to what the Scriptures say should be part of our worship of God. However, the Scriptures that deal in worship do not give us an explicit, step-by-step approach to worship. The Scriptures do not tell us what table we should use in Communion, the type of trays to use, do we use table clothes, etc. We know the sacrament must be done and what elements are contained within and there are key Scriptures we go to that Christ left us that put us in the right-thinking during but there are plenty of details not listed.

What do you do if the Scriptures tell you to do one thing but another would seem to direct us to the opposite?

This is more or less the opposite of adiaphora. Here, we are being explicitly told something.

For starters, make absolutely certain that your interpretation is Scripture-accurate. Do not cut yourself off from the wisdom of those who have gone before you in this (Proverbs 11:14, 15:22, 24:6).

Secondly, make certain you are not only reading the texts involved in their respective contexts correctly but also within the context of the rest of Scripture–use the analogy of Scripture (cross-reference).