As a worldwide public health issue, chronic kidney disease still lacks of effective therapeutic approaches due to the challenges in conventional organ transplantation and dialysis. Renal tissue engineering of-fers an advantageous therapeutic or regenerative option over typical donor organ. However, despite the great progress of decellularized extracellular matrix based scaffold for the renal regeneration, sev-eral safety concerns and complex composition still remain to be addressed. Herein, the extracellular matrix-mimicking hydrogel scaffolds were developed through covalent and physical cross-linking be-tween swim bladder-derived natural collagen (COL) and anti-fibrosis chondroitin sulfate (CS) derivatives. The biomimetic hydrogels showed proper mechanical property, excellent thermal stability and high bio-compatibility both in vitro and in vivo, by altering the mass ratio of COL and CS. When implanted in partially nephrectomized rat model, the 1COL/2CS scaffold enable it recruit more native kidney cells, re-duce the tubular damage, and even induce the regeneration of renal tubular-like tissue and restore renal metabolic function more effectively comparing with the pure 2COL and 2CS scaffold. These results suggest that the biomimetic scaffold is a promising functional platform for treating renal diseases.