As renal fibrosis nanotherapeutics, the endogenous biomaterial melanin not only has natural biocompatibility and biodegradability but also has inherent photoacoustic imaging ability and certain anti-inflammatory effects. These properties determine that melanin can not only as a carrier of medication but also track the biodistribution and renal uptake of drugs in vivo by photoacoustic imaging in real-time. Curcumin is a natural compound with biological activity, which has excellent ROS scavenging ability and good anti-inflammatory property. These materials appear more advantages in the development of nanoscale diagnostic and therapeutic platforms for future clinical translation. Herein, this study developed curcumin-loaded melanin nanoparticles (MNP-PEG-CUR NPs) as an efficient medication delivery system for photoacoustic imaging guidance renal fibrosis treatment. The nanoparticles are about 10 nm in size, exhibit good renal clearance efficiency, excellent photoacoustic imaging ability, and good in vitro and in vivo biocompatibility. These preliminary results indicated that MNP-PEG-CUR have clinically applicable potential as a therapeutic nanoplatform for renal fibrosis.