Erectile Dysfunction (ED) is a prevalent sexual health condition affecting a significant portion of the male population worldwide. The conventional therapeutic approaches for ED often involve the use of pharmaceutical agents targeting the phosphodiesterase-5 (PDE5) enzyme. Currently, treatment with PDE-5 inhibitors is the standard approach for ED, and four PDE-5 inhibitors, namely sildenafil, vardenafil, tadalafil, and avanafil, are in use. However, these pharmaceutical interventions may be associated with adverse effects and limitations. As a result, there has been a growing interest in exploring alternative and complementary treatment options for ED, such as nutraceuticals, which are bioactive compounds derived from natural sources. Nutraceuticals, which include vitamins, minerals, herbs, and other dietary supplements, have gained popularity for their potential health benefits. Certain nutraceuticals have demonstrated the ability to modulate various physiological pathways, including those involved in erectile function. A notable mechanism of action is the inhibition of the PDE5 enzyme, which plays a pivotal role in the regulation of cGMP levels. By inhibiting PDE5, nutraceuticals can promote the accumulation of cGMP, leading to enhanced penile blood flow and improved erectile function. A comprehensive analysis of the literature showcases various nutraceutical agents, including plant-derived compounds like flavonoids, polyphenols, and amino acids which have exhibited PDE5 inhibitory effects. Mechanistic insights into their action involve modulation of NO release, cGMP elevation, and relaxation of penile smooth muscles, all critical factors for achieving and sustaining erections. This review focuses on elucidating the role of nutraceuticals in treating erectile dysfunction through the inhibition of the PDE5 enzyme.