Objective To investigate the clinical effect of edaravone combined with sodium valproate in the treatment of post-stroke epilepsy (PSE) and its influence on neuron-specific enolase (NSE), inflammatory factors, and adverse reactions. Methods A total of 100 patients who were admitted to our hospital from October 2015 to October 2016 were enrolled and randomly divided into control group and observation group, with 50 patients in each group. In addition to conventional treatment, the patients in the control group were given sodium valproate, and those in the observation group were given sodium valproate combined with edaravone. After 1 year of treatment, the two groups were compared in terms of clinical outcome, seizure, NSE, inflammatory factors, and safety. Results After 1 year of treatment, the observation group had a significantly higher overall response rate than the control group (92.0% vs 74.0%, P<0.05). The observation group had a significantly lower number of seizures and a significantly shorter duration of seizures than the control group (P<0.05). After 1 month of treatment, the observation group had a significantly lower level of NSE than the control group (P<0.05), while there was no significant difference between the two groups during the subsequent treatment (P>0.05). The observation group had significantly lower levels of tumor necrosis factor-α, interleukin-2, and interleukin-8 than the control group (P<0.05). There was no significant difference in the incidence rate of adverse reactions between the two groups (24.0% vs 28.0%,P>0.05). Conclusions Edaravone combined with sodium valproate has a marked clinical effect in patients with PSE and can significantly reduce the levels of NSE and inflammatory factors, with good safety.