Abstract: Rheumatoid arthritis (RA) is one of the most prevalent systemic autoimmune inflammatory diseases worldwide, causing chronic, progressively worsening arthritis that may ultimately lead to disability. Despite the availability of numerous therapeutic agents, limitations exhibit, including poor aqueous solubility, suboptimal stability, inadequate permeability, short half-lives, and multi-organ toxicity during long-term or high-dose administration. Nanoparticle-based drug delivery offers a robust strategy to mitigate these deficiencies while maximizing therapeutic efficacy through controlled-release mechanisms and rational administration route design. This review systematically summarizes recent advancements in nanoparticle drug delivery strategies for RA treatment from the perspective of three distinct mechanisms. It details the design rationales, therapeutic principles, and effects of various delivery systems, with particular emphasis on their interactions with the disease microenvironment and the entire body.