Compounds containing thiazole and chalcone privileged scaffolds were reported to possess excellent antitubercular and anticancer activities. Considering the potential activities of these privileged structures, in the present study, we designed, synthesized and characterized a novel series of 2,4-dichlorothiazole-5-carboxaldehyde-derived chalcones (21-40) and evaluated them for antitubercular and antiproliferative activities by employing standard protocols. Among the twenty compounds, chalcones 12 and 7 containing 2,4-difluoro and 2,4-dichloro groups showed potential antitubercular activity higher than the standard pyrazinamide (MIC = 25.34 µM) with MICs 2.43 and 4.41 µM respectively. Chalcone 20 containing heteroaryl 2-thiazolyl moiety exhibited promising antiproliferative activity against the prostate cancer cell line DU-145 higher than the standard methotrexate (IC₅₀ = 11 ± 1 µM) with an IC₅₀ value of 6.86 ± 1 µM. All the compounds were further evaluated for their cytotoxicity against normal human liver cell lines L02 and were found to be non-toxic. Potential activity and non-toxic nature of these compounds advocate that the lead compounds emerged out of this study, pave the way for the development of novel drugs against tuberculosis infections and prostate cancer.