Cell　surface　receptors　are　important　proteins　that　mediate　communication　between　the　cells　and　their　outside　environment,　and　also　play　essential　roles　in　the　control　of　a　wide　variety　of　biological　processes,　such　as　cell　cycle,　proliferation,　communication,　migration　and　apoptosis.　Receptor　oligomerization　is　an　essential　signal　transduction　mechanism　that　cell　surface　receptors　use　to　transmit　extracellular　signals　into　the　internal　cytosol　cellular　machinery.　Therefore,　regulating　receptor　oligomerization　provides　an　opportunity　to　customize　cellular　signaling　and　to　direct　cellular　behavior　in　a　user-defined　manner.　Some　techniques　have　been　developed　for　receptor　oligomerization　regulation,　such　as　chemically　induced　dimerization　(CID)　and　optogenetics,　which　involve　traditional　genetic　engineering.　However,　the　process　of　genetic　manipulation　is　time-consuming,　unpredictable　and　inefficient.　Thus,　development　of　nongenetic　strategies　for　precisely　regulating　receptor　oligomerization　remains　a　desirable　goal.　Recently,　along　with　the　utilization　of　DNA,　protein,　small　molecules　and　stimuli-responsive　materials-based　nongenetic　engineering　strategies,　various　receptor　oligomerization　and　multiple　cellular　behaviors　could　be　regulated,　including　migration,　proliferation,　apoptosis,　differentiation　and　immune　responses,　etc.　In　this　review,　we　aim　to　systematically　introduce　advances　in　the　development　of　nongenetic　engineering　strategies　for　regulating　receptor　oligomerization,　and　provide　insights　into　the　existing　challenges　and　future　perspectives　of　this　field.　This　journal　is　©　2020　The　Royal　Society　of　Chemistry.