The emergence of antibiotic-resistant bacteria poses a critical challenge to global public health, necessitating the exploration of alternative therapeutic strategies. This study investigates the antimicrobial potential of bioactive compounds derived from four medicinal plants: Chrysopogon zizanioides, Asteracantha longifolia, Asparagus racemosus, and Tinospora cordifolia. These plants, traditionally used in various medicinal systems, contain compounds such as khusimol, stigmasterol, lupeol, shatavarin IV, asparagamine A, tinosporin, and cordifolioside A, which have shown promising antimicrobial properties against resistant pathogens. Two formulations were developed: Formulation 1, designed for oral administration, and Formulation 2, a topical cream, both targeting antibiotic-resistant strains like methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Escherichia coli (MDR E. coli). The Minimum Inhibitory Concentration (MIC) of each extract and formulation was determined using a microdilution method. Results indicate that these plant-based formulations exhibit significant inhibitory effects on bacterial growth, with potential applications as complementary therapies to conventional antibiotics. This study highlights the potential of these medicinal plants as sources of novel antimicrobial agents, providing a sustainable approach to combating antibiotic resistance.