Oxadiazoles belong to the group of heterocyclic compounds which contains one oxygen and two nitrogen atoms, forming a five-membered heterocyclic ring. The current research was based on the design, synthesis and pharmacological evaluation of 2-[3-(4-Nitro benzene) propionic acid-5-(Substituted phenyl)-1,3,4-Oxadiazole Derivatives. The novel derivatives of oxadiazole were synthesized by utilizing specific conditions and process and evaluated their physical properties i.e., melting point, RF value, FTIR, NMR, Mass, and Docking studies. The animals were obtained from animal house, Department of Pharmacy, MJPRU Bareilly for in-vivo study. The anxiolytic activity of synthesized novel oxadiazole derivatives were tested by Forced Swimming Test and Locomotor Activity models. In results, in all the models, novel derivatives of 1,3,4-oxadiazole (200mg/kg) significantly demonstrated anxiolytic potential at both the doses when compared to control. In both the doses, it significantly proved for its anxiolytic potential by facilitating the mood of animals. In conclusion, novel derivatives of 1,3,4-oxadiazole is significant anxiolytic synthetic drug. It can be effectively used in the treatment of anxiety, depression, mental agitation and other neurological disorders after successfully evaluating mechanism of action of the synthetic derivatives. It suggests to perform the structure elucidation of synthesized derivatives and develop after structural modification (SAR) in desired dosage form to determine the highest bioavailability, potency, and efficacy (intrinsic activity). It also suggests researchers to determine its mode of action for anxiolytic effect.