A number of new 2,5-disubstituted 1,3,4-thiadiazole and their S- or N-substituted derivatives as well as the corresponding sugar hydrazone derivatives were synthesized and tested for their antimicrobial activity against Bacillus subtilis (Gram-positive), Pseudomonas aeruginosa (Gram-negative), and Streptomyces species (Actinomycetes). The synthesized compounds displayed different degrees of antimicrobial activities or inhibitory actions.