Heterocyclic moiety is a key part of some enzymes and vitamins and plays a vital role in various biochemical and enzymatic processes. Piperazine ring is a heterocyclic moiety present in various well-known drugs and is effective against different types of diseases by acting on a variety of receptors. Various piperazine analogs possess diverse biological activities, especially in central nervous system disorders, which involve the activation of neurotransmitter receptors and targeting various enzymes and act as antianxiety, antipsychotic, antidepressant, etc. This review is focused on the piperazine derivatives and their diverse therapeutic potential against different types of diseases particularly against neuronal disorders.