Objective: To investigate effects of supplementation with a fermented red clover (RC) extract on signaling proteins related to muscle protein synthesis and breakdown at rest and in response to a resistance exercise bout. Methods: Ten postmenopausal women completed a double-blinded cross-over trial with two different intervention periods performed in random order: (A) RC extract twice daily for 14 days, and (B) placebo drink twice daily for 14 days. The intervention periods were separated by a two-week washout period. The each intervention period a muscle tissue sample was obtained before and three hours after a one-legged resistance exercise bout. The strength was assessed before and after each intervention period. Results: Protein expression of FOXO1 and FOXO3a, two key transcription factors involved in protein degradation, were significantly lower and HSP27, a protein involved in cell protection and prevention of protein aggregation was significantly higher following RC extract compared to placebo. The significant treatment × time interaction was observed for muscle protein expression in response to exercise. However, p-mTOR, p-p70S6k and HSP90 protein content were significantly increased in response to exercise in both groups. Conclusions: This study demonstrates that RC extract supplementation downregulates molecular markers of muscle protein degradation compared to placebo in postmenopausal women.