The present study reports the synthesis and pharmacological evaluation of a series of novel acetamide derivatives designed to explore their potential antipsychotic activity. The compounds were synthesized through standard acylation techniques, and their structures were confirmed using FT-IR, ^1H-NMR, ^13C-NMR, and mass spectrometry. The synthesized derivatives were screened using established behavioral models in rodents, including amphetamine-induced hyperlocomotion and apomorphine-induced stereotypy. Several compounds showed significant reductions in hyperactivity and stereotypic movements, indicating possible dopamine receptor antagonism. Catalepsy assessments were performed to evaluate extrapyramidal side-effect liability, and select derivatives exhibited favorable activity with minimal motor impairment compared to reference antipsychotic drugs. Preliminary structure–activity relationship analysis suggested that specific substituent modifications enhanced pharmacological responses. Overall, the findings indicate that these novel acetamide derivatives may serve as promising lead molecules for further development of safer and more effective antipsychotic agents.