Polymeric poly(bile acid) (pBA) nanoparticles have enhanced avidity and affinity to bile acid receptors and are effective anti-inflammatory agents. Oral delivery results in local accumulation and retention in the pancreas, liver, and colon as well as in systemic delivery of the nanoparticles. The nanoparticles are effective in alleviating inflammation and are useful as anti-inflammatory agents to treat inflammatory diseases of the organs. The nanoparticles provide a therapeutic and prophylactic benefit via the TGR5 pathway when used alone, or a more than additive benefit when used in combination with immunosuppressant(s). The nanoparticles induce immune tolerance in autoimmune diseases and are useful therapeutics for treating inflammatory and autoimmune diseases.