Erectile dysfunction (ED) is a common condition among aging men, often associated with metabolic disorders, diabetes mellitus, hypertension, oligozoospermia, cardiovascular disease, sedentary lifestyles, chronic infections, and inflammation. A major therapeutic challenge is the inefficient delivery of drugs to penile smooth muscle tissue. Moreover, synthetic pharmacological treatments frequently cause adverse effects, including off-target interactions and risks to vital organs, especially the heart. As a result, there is growing interest in phytochemicals derived from medicinal plants, which offer natural, cost-effective, and less toxic alternatives. Numerous preclinical and clinical studies have shown that phytochemicals support muscle function through antioxidant and anti-inflammatory properties, modulation of the phosphodiesterase type 5 (PDE5) pathway, and hormone regulation. This review highlights the potential of combining phytochemicals with nanotechnology to develop safer and more effective treatments for penile tissue disorders. We also examine nanomedicine delivery systems such as liposomes, nanoemulsions, and dendrimers that enhance the bioavailability, targeted delivery, and controlled release of these compounds. Overall, this review underscores the promise of phytochemical-based nanomedicine in improving therapies for penile smooth muscle dysfunction.

Keywords: bioactive compounds; erectile dysfunction; nanomedicine; PDE5 signaling; phytochemicals