<p>Healthy aging and longevity are complex processes influenced by genetic, biochemical, physiological, environmental, psychological, emotional and lifestyle factors across various organisms. Among these, nutrition plays a pivotal role and is a focus in various studies due to its potential to extend lifespan. Scientific evidence from signalling pathway research supports the connection between diet, nutritional components and longevity. Many factors have been implicated in aging and age-related diseases. Reactive oxygen species threshold beyond the antioxidant defence system capacity is the principal cause of dysfunctional cellular antioxidant defence system, exacerbating oxidative stress and contributing significantly to aging and age-related diseases such as cancer, cardiovascular disease and diabetes. Mushrooms are nutritionally and therapeutically rich in antioxidants with diverse bioactive constituents that benefit human health. Mushrooms and their components, such as L-ergothioneine, demonstrate antioxidant and anti-aging properties. Mushrooms and components support healthy aging, extend lifespan and promote longevity through their antioxidant and cytoprotective properties, as reported in experimental models of aging in this review. These properties may be linked to the ability to delay the reported hallmark aging mechanisms, including cellular senescence, mitochondrial dysfunction, genomic instability, inflammaging and telomere attrition. This review consolidates current research on the nutritional and pharmacological importance of mushrooms and highlights the need to bridge the gap between bench research and clinical application, with mushrooms and their components, as powerful dietary allies for healthy aging and longevity in the human population.</p>