Neuroinflammation is often characterized by an overactive microglial response. Curcumin, known for its anti-inflammatory and antioxidant properties, can mitigate microglial hyperactivity following epileptic seizures. The study delves into the molecular mechanisms underlying curcumin's modulation of RNA post-transcriptional N (6)-methyladenosine (m6A) modification. It is found that curcumin interacts with the Z1-type protein tyrosine phosphatase receptor (PTPRZ1), maintaining its enzymatic activity and thus regulating the phosphorylation of the m6A-reader YTH domain-containing family protein 2 (YTHDF2). This modulation affects the expression of critical genes, resulting in reduced inflammatory responses. These findings highlight the importance of post-transcriptional modifications of RNA in the neuroprotective and anti-inflammatory effects of curcumin, offering new insights for the treatment of related diseases.