This article proposes a 505-channel pixel-sharing sub-retinal prosthesis (PSRP) system-on-chip (SoC) that aims to effectively restore patients’ visual acuity using the modular active/return electrode (Mod-A/R) scheme to mitigate current scattering and time-based photodiode (T-PD) sensing to increase the dynamic range (DR) of light sensing. To improve stimulation efficiency, the PSRP SoC adopts per-pixel dynamic voltage scaling (DVS) that can adaptively select different optimal supply voltages for each pixel. The proposed PSRP SoC has a small area of 0.01 mm per pixel, while the Mod-A/R scheme reduces the current scattering by up to 95.4%. By combining five pixels into a single structure, the five-pixel sharing set can accommodate the T-PD sensor and the per-pixel DVS. The proposed T-PD sensor with internal clock modulation can detect the light in the range of 0.13–19 klux with a DR of 35.8 dB, while the per-pixel DVS reduces stimulation energy consumption by up to 64%. The PSRP SoC coated with sputtered iridium oxide film (SIROF) electrode can be applied to clinical trials by adapting the light detection range and stimulus intensity with 44-bit external control. Ex vivo experiments with retinal samples of mice have verified the effectiveness of the PSRP SoC. IEEE