Following an initial ankle sprain it is not unlikely that chronic ankle instability (CAI) will develop. CAI is associated with impaired perceived functional and mechanical properties of the ligaments. Nutritional supplementation with collagen peptides has been shown to improve the functional and mechanical properties of the connective tissue. The purpose of this study was to investigate the effectiveness of specific collagen peptide supplementation (SCP) to improve ankle stability in athletes with CAI. 50 male and female athletes with CAI completed a randomized, double-blinded and placebo-controlled study with a daily oral administration of either 5 g SCP or 5 g placebo (Maltodextrin) over a period of six months. Both, the Cumberland Ankle Instability Tool (CAIT) and the German version of the Foot and Ankle Ability Measure (FAAM-G) were used to measure the subjective perceived function of the ankle. Additionally, the mechanical stability was determined by measuring the ankle stiffness by an ankle arthrometer. Finally, a three-month follow-up was performed. ANOVA analysis indicated that the subjective ankle stability was improved in both the CAIT (p < 0.001) and the FAAM-G (p < 0.001) following SCP supplementation compared with placebo. No significant changes between the groups were detected in the results of the ankle arthrometer. After six month the subjective report of the ankle stability function significantly improved and the three month follow-up revealed a significant decline in the number of ankle joint injuries (p < 0.05). These data support the concept that specific collagen peptide supplementation in athletes with chronic ankle instability results in significant improvements in subjective perceived ankle stability. The reduction in the re-injury rate of ankle sprains in the follow-up period suggests that these findings have clinical relevance.