High-density lipoprotein (HDL) has been proposed to provide cardio-protective properties through the functionality of its anti-inflammatory and antioxidant enzymatic machinery. Within this article, the beneficial effects of several functional foods on HDL levels and functionality for cardio-protection are thoroughly reviewed. Emphasis is given to functional foods and their antioxidant and anti-inflammatory health-promoting effects for the cardiovascular system through their benefits on HDL, which act either solely or synergistically as an adjuvant approach with well-established anti-atherogenic therapies. Promising outcomes from both in vitro and in vivo studies in animal models and clinical trials, which outline the beneficial effects of such functional foods on HDL levels and functionality, are thoroughly discussed. The mechanisms of the obtained antioxidant, anti-inflammatory, antithrombotic, and cardio-protective effects on HDL activities of functional foods containing natural bioactives are also outlined. Limitations and future perspectives on the overall benefits that these natural bioactive compounds exert as important ingredients in functional foods to induce HDL-related benefits and to strengthen cardiovascular health are also discussed.