This systematic review summarizes the long-term health benefits of physical activity, focusing on its relationship with weight gain, obesity, coronary heart disease (CHD), type 2 diabetes mellitus (T2DM), and dementia. The study analyzed 15 longitudinal studies with over 288,724 participants, aged 18–85 years, and a minimum of 5 years of follow-up. The findings indicate that physical activity has a positive long-term effect on all these conditions. For weight gain and obesity, higher physical activity levels were associated with lower weight gain. For CHD, physical activity was linked to reduced risk, with a minimum of 1,000 kcal per week of additional energy expenditure needed for health benefits. For T2DM, higher physical activity levels were associated with lower risk, though more intense activity was needed for significant benefits. For dementia and Alzheimer's disease, physical activity was negatively related to incidence, with regular activity showing protective effects. However, the review highlights a lack of long-term studies on the relationship between physical activity and NCDs. The studies included were primarily focused on healthy adults, and there is a need for more research on diverse populations and the causal relationship between physical activity and these diseases. The review also notes limitations, including the use of self-reported data and the lack of studies on non-English publications. Overall, the results suggest that physical activity is an important factor in preventing NCDs and age-related diseases, but more long-term research is needed to fully understand its impact.This systematic review summarizes the long-term health benefits of physical activity, focusing on its relationship with weight gain, obesity, coronary heart disease (CHD), type 2 diabetes mellitus (T2DM), and dementia. The study analyzed 15 longitudinal studies with over 288,724 participants, aged 18–85 years, and a minimum of 5 years of follow-up. The findings indicate that physical activity has a positive long-term effect on all these conditions. For weight gain and obesity, higher physical activity levels were associated with lower weight gain. For CHD, physical activity was linked to reduced risk, with a minimum of 1,000 kcal per week of additional energy expenditure needed for health benefits. For T2DM, higher physical activity levels were associated with lower risk, though more intense activity was needed for significant benefits. For dementia and Alzheimer's disease, physical activity was negatively related to incidence, with regular activity showing protective effects. However, the review highlights a lack of long-term studies on the relationship between physical activity and NCDs. The studies included were primarily focused on healthy adults, and there is a need for more research on diverse populations and the causal relationship between physical activity and these diseases. The review also notes limitations, including the use of self-reported data and the lack of studies on non-English publications. Overall, the results suggest that physical activity is an important factor in preventing NCDs and age-related diseases, but more long-term research is needed to fully understand its impact.