Abstract Background Hepatitis C virus (HCV) infection is still one of the leading causes of chronic liver disease, with chronically infected making up approximately 1% of the global population. Aim and Objectives The aim of this work was to study side effects of directly acting anti HCV drug (DAA) and its progression in metabolism of lipid profile, blood sugar level, and renal function. Subjects and Methods This case study had been carried out on 200 subjects presented to Department of Internal Medicine at Kobbri ELkobba hospital inpatient and outpatient clinics between March 2016 and September 2016. All subjects participating in the study was asked to sign informed concept before inclusion. Results There are non-significant changes in liver enzymes, AST, ALT, INR, and CBC. But in lipid profile, non-significant changes in HDL, But noticed significant decrease in LDL and significant increase in TG from (172.53 ± 36.11) to (267.84 ± 63.24 ) and Total cholesterol, significant increase from (203.60 ± 53.85) to ( 216.15 ±55.67). In HbA1C, there was significant increase. Conclusion Once-daily oral daclatasvir plus sofosbuvir with or without Ribavirin was associated with high rates of sustained virologic response among patients infected with HCV, including chronic cirrhotic patients and relapsers, successful treatment associated with Improvement of liver function parameters in the majority of patients, Increase in urea level, serum creatinin and HbA1C. There is significant decrease in LDL and mild increase in TG level.