Infections, metabolic diseases, and cancer are the primary causes of death worldwide. The lack of efficacy, low selectivity, and emergence of resistance in clinically used medications require the search for new drug candidates. In this study, 3-(1H-indol-3-yl)-1-arylprop-2-en-1-ones and 2-(3-(3-oxo-3-arylprop-1-en-1-yl)-1H-indol-1-yl)-N-(4-sulfamoylphenyl)acetamides were designed and synthesized. Chemical structures of the compounds were elucidated by 1H NMR, 13C NMR, and HRMS. Antibacterial and antituberculosis effects of the compounds were investigated by REMA method. DPPH assay was used to test antioxidant effects. Cytotoxicity experiments were carried out by MTT assay. Chalcone-type compound 5 and sulfonamide derivative compound 9 draw attention with the lowest MIC = 15.62 & mu;g/ml values against M. tuberculosis. Compound 3 was the most potent antibacterial agent against A. baumannii and A. hydrophila, which cause severe infections in immunocompromised persons. Fluorinated chalcone derivatives 3, 4, 5 and sulfonamide derivative compound 8 were the most effective compounds in the series with the lowest MIC value of 62.5 & mu;g/ml against C. albicans. Compounds 6 (IC50 = 13.946 & mu;M) and 10 (IC50 = 18.844 & mu;M) showed antioxidant activity. The sulfonamide derivatives were moderate cytotoxic against Caco-2 cell line, while they had no considerable cytotoxicity against MCF-7 cell lines. The results showed that the most potent sulfonamide-based indole chalcones 9 and 10 were less toxic against non-cancer HUVEC cell compared to 5-FU with IC50 values 110.78 & PLUSMN; 49 & mu;g/ml and 83.44 & PLUSMN; 32 & mu;g/ml. Considering the prominent challenges of drug resistance and low bioavailability in antibacterial and anticancer therapies, the lead compounds investigated in this work possess potential for the development of innovative chemotherapeutic agents.