Heart failure is increasingly prevalent in terms of mortality and morbidity worldwide, with myocardial infarction (MI) being a significant contributor. This work presents lisinopril (LN) and tannic acid (TA)-loaded nanoparticles (LNTA NPs), tailored for the pathological features of acute MI. The particle diameter of TA NPs was 325 nm with a polydispersity index of 0.002. Consequently, a fucoidan (Fu)/collagen (Col) hydrogel (HGL) exhibiting favorable mechanical and biological properties has been developed, with LNTA NPs integrated into the HGL-LNTA, resulting in several synergistic therapeutic effects. The incorporation of Fu enhanced the injectability and mechanical strength of the HGL, while endowing the Col material with anticoagulant characteristics vital for prospective clinical applications as cardiovascular biomaterials. LNTA NPs decreased the production of reactive oxygen species (ROS) and enhanced the activities of superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GPx). The LNTA NPs, administered directly to the infarct site, not only provide mechanical support but also significantly restore cardiac function (***p < 0.001) and protect myocardial tissue by scavenging ROS and alleviating inflammation. Collectively, our results have validated the superior therapeutic efficacy of HGL-LNTA in treating MI patients, positioning it as a promising strategy for MI management.