Cardiovascular disease is one of the leading causes of mortality worldwide, primarily driven by atherosclerosis, a chronic inflammatory condition contributing significantly to fatalities. Various biological determinants affecting cardiovascular health across different age and sex groups have been identified. In this context, recent attention has focused on the potential therapeutic and preventive role of increasing circulating levels of heat shock protein 27 (plasma HSP27) in combating atherosclerosis. Plasma HSP27 is recognized for its protective function in inflammatory atherogenesis, offering promising avenues for intervention and management strategies against this prevalent cardiovascular ailment. Exercise has emerged as a pivotal strategy in preventing and managing cardiovascular disease, with literature indicating an increase in plasma HSP27 levels post-exercise. However, there is limited understanding of the impact of exercise on the release of HSP27 into circulation. Clarifying these aspects is crucial for understanding the role of exercise in modulating plasma HSP27 levels and its potential implications for cardiovascular health across diverse populations. Therefore, this review aims to establish a more comprehensive understanding of the relationship between plasma HSP27 and exercise.