Background <p>Polydopamine nanoparticles (PDA NPs) hold considerable significance in biomedical field due to their diverse multifunctionality, including efficient metal ion chelation, intrinsic antioxidant activity, and robust photothermal properties. Especially, ultrasmall PDA NPs can evade rapid liver and spleen accumulation, enabling multi-organ distribution and wide biological applications. However, current methods for synthesizing ultrasmall PDA NPs face the bottleneck of complex synthesis processes.</p> Methods <p>We showed an alkali-controlled one-pot synthesis of ultrasmall PEGylated PDA (UPPDA) NPs. Upon Mn²⁺ chelation, the resulting PDA-PEG-Mn (PPMn) NPs were employed for contrast-enhanced magnetic resonance imaging (MRI) in multiple systemic diseases, including glioma (a nervous system disease), carotid artery stenosis (a circulatory system disease), and acute kidney injury (a urinary system disease). Furthermore, UPPDA NPs were utilized for antioxidant treatment and photothermal therapy at the cellular level.</p> Results <p>PPMn NPs enable precise diagnosis of glioma, carotid artery stenosis, and acute kidney injury through MRI. Additionally, UPPDA and PPMn NPs exhibit outstanding antioxidant properties and demonstrate effective photothermal ablation capabilities at the cellular level.</p> Conclusions <p>The proposed UPPDA NPs provide a universal platform for the diagnosis and treatment of various diseases.</p> Graphical abstract <p></p>