Objective： To analyze the effectiveness of a combination therapy of methylprednisolone and doxycycline in children with Mycoplasma pneumoniae pneumonia and to explore its impact on inflammatory factors and oxidative stress indicators. Methods: A total of 200 children with Mycoplasma pneumoniae pneumonia treated in our hospital from May 2021 to May 2023 were selected and randomly divided into two groups. The control group (n=100) received doxycycline monotherapy, while the observation group (n=100) received a combination therapy of methylprednisolone and doxycycline. The therapeutic effects, levels of inflammatory factors, oxidative stress levels, and adverse drug reactions were compared between the two groups. Results: After a two-week treatment period, the overall effective rate of treatment in the observation group was higher than that in the control group. Levels of inflammatory factors (CRP,TNF-α, IL-8) in the observation group were lower than those in the control group. Oxidative stress indicators showed that LPO levels were lower, while ALB and TBIL levels were higher in the observation group compared to the control group. These differences were statistically significant (P<0.05). However, there was no statistical significance in the comparison of adverse drug reactions between the two groups (P>0.05). Conclusion: The combination therapy of methylprednisolone and doxycycline effectively regulates the levels of inflammatory factors and oxidative stress indicators in children with Mycoplasma pneumoniae pneumonia, achieving remarkable therapeutic effects with high safety.