This systematic review was conducted in accordance with the PRISMA guidelines to summarize the existing literature on the effects of different exercise interventions on cardiac autonomic control and secondary health factors. Resting heart rate variability (HRV) was used as indicator of cardiac autonomic control. Secondary factors were related to factors that contribute to cardiovascular health. Studies examining the effects of endurance, resistance, multimodal, or coordinative training interventions in healthy participants aged between 45 and 60 years old on average were considered. The methodological quality of the studies was examined using two assessment scales (TESTEX and STARD(HRV)). PROSPERO registration number: CRD42020206606. The literature review retrieved eight studies fulfilling all inclusion criteria. Cardiac autonomic control and cardiovascular health improved after endurance and multimodal interventions. Resistance training had no significant impact on HRV or any secondary health factor. Coordinative exercise interventions showed inconclusive results regarding HRV but showed significant improvements in secondary health factors. The quality assessment tools revealed some methodological and reporting deficits. Despite the small number of studies, we suggest endurance and multimodal interventions including aerobic exercises for the enhancement of cardiac autonomic control and the reduction of cardiovascular risk in middle-aged adults. Further studies need to be conducted to examine the long-term effects of exercise in the midlife period.