The natural limonoids distributed mainly in the Meliaceae and Rutaceae plants are known for their unique and complex structure with high degree oxidation and cyclic rearrangement. However, these compounds exhibit a broad range of biological activities such as insecticidal, antibacterial, antifungal, antimalarial, antioxidant, anticancer, antiviral, and anti-inflammatory. There is still limited report about the biological activity of the anti-inflammatory effect of limonoids isolated from plants. Therefore, this study aimed to examine the effect of intact, deformed and rearranged limonoids as anti-inflammatory agents. The majority of anti-inflammatory investigations were evaluated by in vitro and in vivo assays of the isolated pure compounds and their derivatives. For the in vitro study, intact and C-ring seco limonoids showed a potent inhibitory effect against NO production. The in vivo analysis of Intact, C-seco, and AD-seco limonoids showed a potent effect based on the inhibition of pro-inflammatory cytokines expression, indicating their potency as anti-inflammatory agents.