Cardiovascular diseases pose a significant global health challenge, contributing to high mortality rates and impacting overall well-being and quality of life. Nitric oxide (NO) plays a pivotal role as a vasodilator, regulating blood pressure and enhancing blood flow—crucial elements in preventing cardiovascular diseases, making it a prime therapeutic target. Herein, metal-based nanozymes (NZs) designed to induce NO release from both endogenous and exogenous NO-donors are investigated. Successful synthesis of gold, platinum (Pt) and cerium oxide NZs is achieved, with all three NZs demonstrating the ability to catalyze the NO release from various NO sources, namely S-nitrosothiols and diazeniumdiolates. Pt-NZs exhibit the strongest performance among the three NZ types. Further exploration involved investigating encapsulation and coating techniques using poly(lactic-co-glycolic acid) nanoparticles as experimental carriers for Pt-NZs. Both strategies showed efficiency in serving as platforms for Pt-NZs, successfully showing the ability to trigger NO release.