Serotonin (5-hydroxytryptamine, 5-HT) is a key neurotransmitter involved in the regulation of mood, cognition, perception, sleep, and behavior. Dysregulation of serotonergic signaling has been strongly implicated in the pathophysiology of several neuropsychiatric disorders, including schizophrenia, depression, anxiety disorders, bipolar disorder, and migraine. Serotonin antagonists act by selectively or non-selectively blocking specific 5-HT receptor subtypes, thereby modulating abnormal neurotransmission associated with these conditions. Notably, antagonism at 5-HT₂A and 5-HT₂C receptors has shown therapeutic benefits in the management of psychosis, mood instability, and behavioral disturbances, while also reducing extrapyramidal side effects when used in antipsychotic therapy. This review focuses on the pharmacological basis of serotonin antagonists, their receptor-specific actions, and their clinical relevance in various neuropsychiatric disorders. Recent advances, therapeutic applications, and future prospects of serotonin antagonists in neuropsychiatry are also discussed. Keywords:Serotonin antagonists; 5-HT receptors; Neuropsychiatric disorders; Antipsychotic therapy; Mood disorders; Neurotransmission