Pharmaceutical pollution is an emerging threat to aquatic ecosystems and public health, owing to the persistence, toxicity, and bioaccumulation potential of many synthetic active compounds. This chapter explores the potential of green alternatives based on natural plant-derived compounds such as flavonoids, alkaloids, terpenoids, tannins, and phytosterols as partial or total substitutes for conventional pharmaceuticals. Through case studies, it highlights bioactive molecules with proven pharmacological effects (e.g., quercetin, curcumin, artemisinin) that exhibit favorable environmental profiles, including rapid biodegradation and low aquatic toxicity. The chapter also examines key technical, economic, and regulatory challenges for their implementation, along with the opportunities presented by green chemistry, biotechnology, and circular economic approaches. It concludes that the rational development and use of these alternatives could significantly reduce the burden of emerging contaminants, promoting a more sustainable and responsible pharmacology.