The aryl hydrocarbon receptor (AhR) is a transcript factor, belonging to the basic helix-loop-helix-Per-ARNT-SIM family, is closely associated with health and diseases. Targeting AhR is an emerging therapeutic strategy for various diseases. Norisoboldine (NOR), which is the main alkaloid of Linderae Radix, has been known to activate AhR. Unfortunately, the oral bioavailability (F) of NOR is only 2.49%. To improve the chemical efficacy and bioavailability, we designed and synthesized NOR analogues. Using various in vitro assays, 2-methoxy-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-9-ol (III11) was discovered as a potent AhR agonist. Compound III11 enhanced the expression of AhR downstream target genes, triggered AhR nuclear translocation, and promoted differentiation of regulatory T cells. More importantly, III11 exhibited good bioavailability (F = 87.40%) and remarkable therapeutic effects in a mouse model of ulcerative colitis at a dosage of 10 mg/kg. These findings may serve as a reference for the design of novel AhR agonists against immune and inflammatory diseases.