A series of structurally new, 2-(5-substituted-2,3-dioxoindolin-1-yl)ethyl/propyl 4-(3,4-dichlorophenyl) piperazine-1-carbodithioate derivatives 5a–j were designed and synthesized by conventional technique as well as ultrasound irradiation. All the new compounds were characterized by spectral and elemental analyses. Furthermore, they were evaluated for their in vitro antibacterial, antifungal, antitubercular, and antimalarial activities. The results indicated that some of the synthesized compounds posses promising antimicrobial activity against some grampositive and gram-negative bacteria. Compounds 5b, 5d, and 5e displayed the highest inhibition (99 %) in the range of 3.10–6.25 lg/ml against Mycobacterium tuberculosis H37 Rv, while compounds 5b–g displayed promising antimalarial activity in the range of 0.043–0.092 lg/mL against Plasmodium falciparum 3D7. Thus, these molecules can provide prospective leads in chemotherapy against tuberculosis and malaria.