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Inflammaging, a coexistence of inflammation and aging, is a persistent, systemic, low-grade inflammation seen in the geriatric population. Various natural compounds have been greatly explored for their potential role in preventing and treating inflammaging. <i>Withania somnifera</i> has been used for thousands of years in traditional medicine as a nutraceutical for its numerous health benefits including regenerative and adaptogenic effects. Recent preclinical and clinical studies on the role of <i>Withania somnifera</i> and its active compounds in treating aging, inflammation, and oxidative stress have shown promise for its use in healthy aging. We discuss the chemistry of <i>Withania somnifera</i>, the etiology of inflammaging and the protective role(s) of <i>Withania somnifera</i> in inflammaging in key organ systems including brain, lung, kidney, and liver as well as the mechanistic underpinning of these effects. Furthermore, we elucidate the beneficial effects of <i>Withania somnifera</i> in oxidative stress/DNA damage, immunomodulation, COVID-19, and the microbiome. We also delineate a putative protein–protein interaction network of key biomarkers modulated by <i>Withania somnifera</i> in inflammaging. In addition, we review the safety/potential toxicity of <i>Withania somnifera</i> as well as global clinical trials on <i>Withania somnifera</i>. Taken together, this is a synthetic review on the beneficial effects of <i>Withania somnifera</i> in inflammaging and highlights the potential of <i>Withania somnifera</i> in improving the health-related quality of life (HRQoL) in the aging population worldwide.