With more and more engineered nanoparticles being translated to the clinic, FDA has recently issued a draft guidance on nanomaterial-containing drug products with an emphasis on understanding their in vivo transport and nano-bio interactions in the physiological environment; so that nanoparticles can be designed in a way that they can target and treat diseases more efficiently than small molecules, have minimum accumulation in the normal tissues and organs and induce minimum toxicity and health hazards. In this review, we integrate this guidance with our ten-year studies on developing renal clearable luminescent gold nanoparticles. These gold nanoparticles highly resist serum protein adsorption, escape the liver uptake, target cancerous tissues through enhanced permeability and retention (EPR) effect, and report kidney dysfunction at early stages. In the meantime, "off-target" gold nanoparticles can be eliminated through the kidneys with minimum accumulation in the body. This revisit also allows us to identify future work towards the translation of renal clearable gold nanoparticles from bench to clinics.