Chronic inflammatory diseases, including rheumatoid arthritis, inflammatory bowel disease, type 2 diabetes mellitus, cardiovascular disease, and neurodegenerative disorders, represent a formidable global health challenge, collectively affecting hundreds of millions of individuals and imposing substantial socioeconomic burdens on healthcare systems worldwide. Conventional pharmacological approaches, including nonsteroidal anti-inflammatory drugs, corticosteroids, and biologic agents, although clinically effective in the short term, are associated with significant adverse effects, high treatment costs, and limitations in long-term safety profiles, necessitating the exploration of safer, cost-effective, and mechanistically diverse therapeutic alternatives. This review critically examines the role of phytochemicals, bioactive plant-derived compounds encompassing flavonoids, polyphenols, alkaloids, and terpenoids, as promising candidates for the management of chronic inflammatory diseases. We evaluate the molecular and cellular mechanisms through which these compounds modulate key inflammatory pathways, including the nuclear factor kappa B (NF-kB) signalling cascade, the mitogen-activated protein kinase (MAPK) pathway, the NLRP3 inflammasome, and JAK-STAT signalling, alongside their capacity to suppress proinflammatory cytokine expression, reduce oxidative stress, and restore immune homeostasis. Preclinical evidence from in vitro and in vivo models is systematically discussed alongside emerging clinical data. Challenges in bioavailability, standardization, pharmacokinetic variability, and regulatory compliance are addressed in the context of novel drug delivery strategies, including nanoparticulate formulations and lipid-based carriers. This review underscores the translational relevance of phytochemicals and advocates for rigorous, well-designed clinical trials to substantiate their therapeutic integration into mainstream anti-inflammatory medicine.