The synthesis of new alkanoylated 4-methylphenyl sulphonamoyl carboxylic acids, their molecular docking, and antimicrobial and antioxidant activities were reported. The process involved the mild reaction of acetic anhydride and sodium acetate with 4-methylsulphonamoyl carboxylic acids. The characterization of the compounds was done using FTIR, 1H-NMR, 13C-NMR, and elemental analysis. They were tested for their antimicrobial activities against selected human pathogens such as Pseudomonas aeruginosa, Salmonella typhi, Candida albicans, Aspergillusniger, Staphylococcus aureus, Escherichia coli, and Bacillus subtilis. The antioxidant study of the compounds was evaluated in vitro by the inhibition of generated stable 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical. The in silico study was carried out in order to study five different prevalent disease conditions, namely: bacterial infections, fungal infections, oxidative stress, trypanosomiasis, and malaria. The findings demonstrated that compounds 2b and 2c exhibited the best in vitro antibacterial and antifungal activities compared to ofloxacin and fluconazole. The antioxidant study revealed that compound 2a was the most excellent antioxidant agent. The molecular docking study revealed that compounds 2a, 2b, 2c, 2e, and 2f exhibited excellent antibacterial, antifungal, antioxidant, antitrypanosomal, and antimalaria activities compared to the corresponding standard drugs such as Penicillin, Ketoconazole, α-Tocopherol, Melarsoprol, and Chloroquine, respectively. The physicochemical evaluations showed that all the compounds were drug-like according to “Lipinski’s rule of five”.The synthesized compounds were found to be potent antibacterial, antifungal, antioxidant, and antitrypanosomal agents.