New 5,7-diaryl-4,4-dimethyl-4,5,6,7-tetrahydropyridino[3,4-d]-1,2,3-thiadiazoles 23–27 are synthesized, characterized by melting point, elemental analysis, magnetic spectroscopy (MS), Fourier-transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR) (1 H and 13C) spectra and evaluated for their in vitro antibacterial and antifungal activities. Compounds 23–27 are more potent against Gram-positive bacterial strains, namely Staphylococcus aureus and b-Haemolytic streptococcus. However compounds 23–27 possess potent activity against Klebsiella pneumonia, a Gram-negative bacterial strain, compared to the standard drug used, ciprofloxacin. In general, all the synthesized compounds exert a wide range of modest in vitro antifungal activity against Rhizopus and Microsporum gypsuem than the standard drug, fluconazole.