A series of analogue and derivatives of heterocyclic bearing nitrogen, oxygen, sulphur and oxazole moiety constitutes the core structure of a several biological active compounds. Benzoxazole nucleus containing heterocyclic compounds plays an important role in medicinal chemistry and exhibit wide range of biological activities such as antihyperglycaemic, antidepressant, antibacterial, antifungal, antiinflammatory, antispasmodic, antiallergic and antiasthemetic activity. The present study describes the design, synthesis and in vivo testing of new series of benzoxazole derivatives (S-benzo[d]oxazol-2-yl-2-(4-((2,4-dioxothiazolidin-5-ylidene)methyl)-N-phenylphenylsulfonamido)ethanethioate)) as antihyperglycaemic agents in alloxan induced diabetic Wistar albino rats. Pioglitazone used as a standard drug. Most of the compounds showed significant antihyperglycaemic activity when compared with the standard drug pioglitazone. The structures of all synthesized compounds were determined by their IR, 1H NMR and MASS spectral analysis.