The study aimed to provide evidence on the impact of indoor cycling (IC) in reducing cardiometabolic risk factors. The study compares the effects of a 3 month IC program involving three 55 min sessions per week on women aged 40–60 years, with obesity (OW, n = 18) vs. women with normal body weight (NW, n = 8). At baseline and at the end of the study, anthropometric parameters, oxygen uptake (VO2 peak), and serum parameters: glucose, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), insulin, human anti-oxidized low-density lipoprotein antibody (OLAb), total blood antioxidant capacity (TAC), thiobarbituric acid reactive substances (TBARS), endothelial nitric oxide synthase (eNOS), C-reactive protein (CRP), lipid accumulation product (LAP), and homeostasis model assessment of insulin resistance index (HOMA IR) were determined. Before the intervention, VO2 peak and HDL-C levels were significantly lower and levels of TG, LAP, insulin, HOMA-IR, and CRP were significantly higher in the OW group compared to those in the NW group. After the intervention, only the OW group saw a decrease in body mass, total cholesterol, OLAb, TBARS, and CRP concentration and an increase in total body skeletal muscle mass and HDL-C concentration. In response to the IC training, measured indicators in the OW group were seen to approach the recommended values, but all between-group differences remained significant. Our results demonstrate that IC shows promise for reducing cardiometabolic risk factors, especially dyslipidemia. After 12 weeks of regular IC, the metabolic function of the OW group adapted in many aspects to be more like that of the NW group.