Background In the treatment of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), the antimalarial drug hydroxychloroquine (HCQ) is frequently used. It reduces the risk of illness flare-ups, prevents thrombosis, and lowers the possibility of long-term organ damage. HCQ's advantageous impact on cholesterol levels and diabetes risk reduction. Objective: The aim of the present study was to identify the efficacy of HCQ in rheumatic diseases and associated comorbidities. Patients and method: This cross-sectional study included a total of 71 RA and 9 SLE patients, attending at Department of Rheumatology, Rehabilitation and Physical Medicine, Assiut University Hospitals. University Hospitals. All patients subjected to complete history taking including medication history [HCQ dose (daily, cumulative) and duration], clinical examination, disease activity of RA was defined by DAS 28 (Disease activity scale) and disease activity of SLE by SELDAI-2K (Systemic Lupus Erythematosus Disease Activity Index). Laboratory assessments were performed including: routine investigation, autoantibodies Results: HCQ has a role in control diabetes mellitus (DM) of our diabetic patients and had role in reducing the risk for atherosclerosis and a significant reduction in the lipid profiles as well as AI has been observed. Conclusion: It could be concluded that HCQ is associated with a reduced risk of rheumatic diseases and its associated comorbidities.