This study investigates the use of monascus pigment (MP) nanoparticles (PPM) encapsulated in injectable hydrogels (HY) to improve the microenvironment and enhance the transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) for treating heart failure (HF). The HY is synthesized using Schiff base cross-linking of oxidized hyaluronic acid (OHA) and dopamine-modified hyaluronic acid (HADop) with carboxymethyl chitosan (CMC). PPM, loaded with MP, is designed to scavenge reactive oxygen species (ROS) and regulate macrophage phenotype, thereby improving BMSC survival and activity in the HF microenvironment. The HY demonstrates superior biocompatibility, injectability, and tissue adhesion. In vivo studies in rats with HF showed that HY@PPM effectively reduced intracellular and extracellular ROS levels, decreased inflammation, and prolonged BMSC retention in the pericardium. The combination of HY@PPM and BMSCs significantly improved cardiac function, reducing ventricular remodeling and fibrosis. These findings suggest that HY@PPM has potential as a therapeutic agent for HF by enhancing the microenvironment and preserving BMSC function.This study investigates the use of monascus pigment (MP) nanoparticles (PPM) encapsulated in injectable hydrogels (HY) to improve the microenvironment and enhance the transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) for treating heart failure (HF). The HY is synthesized using Schiff base cross-linking of oxidized hyaluronic acid (OHA) and dopamine-modified hyaluronic acid (HADop) with carboxymethyl chitosan (CMC). PPM, loaded with MP, is designed to scavenge reactive oxygen species (ROS) and regulate macrophage phenotype, thereby improving BMSC survival and activity in the HF microenvironment. The HY demonstrates superior biocompatibility, injectability, and tissue adhesion. In vivo studies in rats with HF showed that HY@PPM effectively reduced intracellular and extracellular ROS levels, decreased inflammation, and prolonged BMSC retention in the pericardium. The combination of HY@PPM and BMSCs significantly improved cardiac function, reducing ventricular remodeling and fibrosis. These findings suggest that HY@PPM has potential as a therapeutic agent for HF by enhancing the microenvironment and preserving BMSC function.