Background Accumulating evidence shows that physical exercise has a positive effect on the release of neurotrophic factors and myokines. However, evidence regarding the optimal type of physical exercise for these release is still lacking. The aim of this study was to assess the acute and chronic effects of open-skill exercise (OSE) compared to closed-skill exercise (CSE) on serum and plasma levels of brain derived neurotrophic factor (BDNFS, BDNFP), and serum levels of insulin like growth factor 1 (IGF-1), and interleukin 6 (IL-6) in healthy older adults. Methods To investigate acute effects, thirty-eight participants were randomly assigned to either an intervention (badminton (aOSE) and bicycling (aCSE), n  = 24, 65.83 ± 5.98 years) or control group (reading (CG), n  = 14, 67.07 ± 2.37 years). Blood samples were taken immediately before and 5 min after each condition. During each condition, heart rate was monitored. The mean heart rate of aOSE and aCSE were equivalent (65 ± 5% of heart rate reserve). In a subsequent 12-week training-intervention, twenty-two participants were randomly assigned to either a sport-games (cOSE, n  = 6, 64.50 ± 6.32) or a strength-endurance training (cCSE, n  = 9, 64.89 ± 3.51) group to assess for chronic effects. Training intensity for both groups was adjusted to a subjective perceived exertion using the CR-10 scale (value 7). Blood samples were taken within one day after the training-intervention. Results BDNFS, BDNFP, IGF-1, and IL-6 levels increased after a single exercise session of 30 min. After 12 weeks of training BDNFS and IL-6 levels were elevated, whereas IGF-1 levels were reduced in both groups. However, only in the cOSE group these changes were significant. We could not find any significant differences between the exercise types. Conclusion Our results indicate that both exercise types are efficient to acutely increase BDNFS, BDNFP, IGF-1 and IL-6 serum levels in healthy older adults. Additionally, our results tend to support that OSE is more effective for improving basal BDNFS levels after 12 weeks of training.