Training in hypoxic environments enhances endurance, but the various influences of training protocols and supplementation for efficient performance are not yet clear. This systematic review explored the effects of different supplementations and interventions used to optimize the aerobic and anaerobic performance of cyclists. Data were collected from the following sources: PubMed, Google Scholar, EMBASE, WOS, Cochrane Central Register of Controlled Trials, and randomized controlled trials (RCTs). Studies that explored the effects of supplementation or intervention during cycling were selected for analysis. Five studies (67 male cyclists; mean age, 23.74–33.56 years) reported different outcomes from supplementation or intervention during the acute hypoxia of cyclists. Three studies (42 male cyclists; mean age, 25.88–36.22 years) listed the benefits of beetroot juice in preserving SpO₂ (pulse oxygen saturation) and enhancing high-intensity endurance performance, effectively preventing the reduction in power output. This systematic review provided evidence that the different effects of ischemic preconditioning (IPC), sildenafil, and beetroot (BR) supplementation and intervention did not present a statistically greater benefit than for normoxia groups, but BR supplementation promoted the benefits of SpO₂. Future research should evaluate the duration and higher FiO₂ (simulated altitude, hypoxia) levels of hypoxia in training protocols for cyclists. This is important when determining the effectiveness of supplements or interventions in hypoxic conditions and their impact on sports performance, particularly in terms of power output.