This study presents luminescent porous silicon nanoparticles (LPSiNPs) that can be used for in vivo applications, such as drug delivery and imaging. LPSiNPs are biodegradable and can self-destruct into renally cleared components, reducing the risk of unintended toxicity. The nanoparticles exhibit intrinsic near-infrared photoluminescence, enabling both accumulation and degradation monitoring in vivo. They can be loaded with therapeutic agents, such as doxorubicin (DOX), and show slow release over time. In vitro and in vivo studies demonstrate that LPSiNPs are non-toxic and can accumulate in MPS-related organs, which are cleared from the body within a week. The nanoparticles also show potential for tumor imaging, as they accumulate in tumors and can be detected using near-infrared fluorescence imaging. Overall, LPSiNPs represent a promising multifunctional nanostructure with a low-toxicity degradation pathway for in vivo applications.This study presents luminescent porous silicon nanoparticles (LPSiNPs) that can be used for in vivo applications, such as drug delivery and imaging. LPSiNPs are biodegradable and can self-destruct into renally cleared components, reducing the risk of unintended toxicity. The nanoparticles exhibit intrinsic near-infrared photoluminescence, enabling both accumulation and degradation monitoring in vivo. They can be loaded with therapeutic agents, such as doxorubicin (DOX), and show slow release over time. In vitro and in vivo studies demonstrate that LPSiNPs are non-toxic and can accumulate in MPS-related organs, which are cleared from the body within a week. The nanoparticles also show potential for tumor imaging, as they accumulate in tumors and can be detected using near-infrared fluorescence imaging. Overall, LPSiNPs represent a promising multifunctional nanostructure with a low-toxicity degradation pathway for in vivo applications.