Plant secondary metabolites possess diverse antimicrobial properties which are exploited in traditional medicine for millennia. Five major phytochemical classes such as alkaloids, flavonoids, phenolic compounds, organosulfur compounds and tannins are analyzed with respect to their antimicrobial activity. Documented mechanisms of action include inhibition of bacterial topoisomerases and DNA gyrase, disruption of cell membrane integrity, interference with energy metabolism, iron chelation and suppression of virulence factors and biofilm formation. Quantitative evidence demonstrates that numerous phytochemicals achieve Minimum Inhibitory Concentrations (MICs) comparable to or superior to conventional antibiotics, with several compounds displaying synergistic potential when combined with standard antimicrobial agents. Structure-activity relationships have been elucidated for flavonoids and alkaloids, facilitating rational design of more potent derivatives. Despite considerable promise in preclinical investigations and agricultural applications, translation to human clinical therapeutics remains limited due to bioavailability constraints, lack of standardization, and insufficient large-scale clinical trials. Thus, this paper is an attempt to examine the efficacy, mechanisms of action and therapeutic potential of phytochemicals against bacterial, fungal and viral pathogens.