Viral infections continue to impose a substantial burden on global public health, contributing to millions of deaths annually and challenging healthcare systems worldwide. Despite advances in antiviral therapeutics, limitations such as drug resistance, narrow spectrum of activity, adverse effects, and high costs necessitate the exploration of alternative therapeutic strategies. Plant-derived natural products represent a rich reservoir of bioactive compounds with diverse structural scaffolds and pharmacological properties that have been utilized in traditional medicine systems for centuries. This review examines the current state of knowledge regarding the isolation, characterization, and development of plant-derived compounds as antiviral agents. Key themes include the systematic screening and selection of phytochemicals with antiviral activity, elucidation of their mechanisms of action targeting viral entry, replication, assembly, and release, as well as modulation of host immune responses. We analyze preclinical evidence from in vitro and in vivo studies demonstrating the efficacy of selected compounds against a range of viral pathogens, including influenza, herpes simplex virus, human immunodeficiency virus, hepatitis viruses, and emerging viruses such as severe acute respiratory syndrome coronavirus 2. Clinical evidence from human trials, structure–activity relationships, formulation strategies to enhance bioavailability, safety considerations including toxicity profiles and herb–drug interactions, and regulatory challenges are critically discussed. This comprehensive analysis provides insights into translational opportunities and future directions for integrating plant-based antiviral compounds into mainstream drug development pipelines, emphasizing the need for standardized methodologies, rigorous clinical evaluation, and collaborative interdisciplinary approaches.