Due to their inherent tunable spectrum, high brightness, excellent biostability and biocompatibility, and functionalization of surfaces, semiconducting polymer dots (Pdots) are now playing an essential role in fluorescent (FL) imaging and disease treatment through bioconjugation with peptides or biomimetic materials. In particular, biomimetic Pdots exhibit their capability in targeted imaging of lesion and increased efficacy for targeting disease treatment. This review will inspect the recent advances in the design and functionalization strategies of biomodified and biomimetic Pdots for enhanced disease detection and therapy. More importantly, the application of these two modifications in targeted FL imaging and cancer treatment is to be addressed in detail. Meanwhile, the main challenges and prospects of biomimetic and biomodified Pdots are to be discussed, which will pave a new avenue for improved disease detection and imaging‐guided treatment.