Antimicrobial resistance (AMR) is rapidly growing worldwide and becoming a well-being threat. It challenges the consumption of antibiotics and eventually jeopardises the management of diseases. Excessive use of antibiotics led to the development of pathogens that are resistant towards multiple drugs. Ocimum species (Tulsi) is known for their potent antimicrobial efficacy and for traditional pharmaceutical applications. It also holds a revered status in Ayurveda and was used to treat various diseases like respiratory, digestive issues, skin infections and stress-related disorders due to its rich phytochemical content that includes ursolic acid, flavonoids, eugenol, rosmarinic acid and essential oils. These bioactive compounds exhibit antimicrobial efficacy against pathogenic microbes. Mechanistically, its metabolites disrupt the microbial cell membranes, inhibit quorum sensing (QS), suppress the production of critical enzymes like β-lactamases, inhibit the formation of biofilm, thus making pathogens more susceptible to antibiotics. Notably, eugenol has been demonstrated to be effective against methicillin-resistant Staphylococcus aureus (MRSA), whereas linalool and thymol show efficacy against extended-spectrum β-lactamase (ESBL)-producing Escherichia coli. The main objective of this study is to seek and elucidate the possible mechanism of action and potential of Ocimum as sustainable next-generation antimicrobial agents, where Ocimum-based treatments represents "One Health" approach that could provide safe and natural ways to fight against AMR in humans and animals.