A novel series of cyanopyridinyl tetrahydronaphthalene incorporated with different heterocycles were synthesized. The key compounds 2a,b were condensed with chloroacetone and ethyl chloroacetate to give 3a,b and 4a,b, respectively. Also condensation of 4a,b with hydrazine hydrate gave the corresponding hydrazide 5a,b. Reaction of 5b with different isothiocyanates gave the corresponding thiosemicarbazide derivatives 6a-c. Also, condensation of 5a with chloroacetic acid, methyl iodide and/or acetic anhydride yielded 7- 9, respectively. Moreover, reaction of 5a with acetylacetone, ethyl acetoacetate, diethylmalonate, ethyl cyanoacetate, chloroacetone, ethyl chloroacetate, urea, phthalic anhydride, malic anhydride and/ or different aldehydes yielded the corresponding derivatives 10-18, respectively. Newly synthesized compounds were screened for their antibacterial (Staphylococcus aureus, Bacillus subtilis, Bacillus megaterium, Sarcina lutea, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli) and antifungal (Saccharomyces cerevisiae and Candida albicans) activity. The results revealed that some of novel compounds have exhibited significant biological activity against the tested microorganisms.