Osteoarthritis is a prevalent chronic health condition that is mostly associated with the degeneration of joint cartilage due to aging or abnormal mechanical stress in the joint. Intraarticularly injected nanoparticle-based lubricants decrease the friction between damaged cartilage surfaces, thus preventing their further degradation; however, the effectiveness of currently used nanoparticle-based lubricants is limited by their short retention time in the joint space. To address this challenge, cationically modified biosourced phytoglycogen nanolubricants are utilized, which electrostatically bind to the cartilage components. The conjugation of the nanoparticles with red-emissive fluorescent carbon dots enables in vivo studies of their retention in the joint. The hytoglycogen nanoconjugates exhibit high colloidal stability in physiological conditions, provide a friction coefficient of 10−3–10−2 between the sliding surfaces under physiologically relevant pressures, strongly bind to the major cartilage surface components, and show significantly prolonged retention time in the joint in vivo, with a fourfold increase in half-life in comparison with conventionally used hyaluronic acid injectant. These properties make these functionalized phytoglycogen nanoparticles a highly promising candidate for joint lubrication.