Visceral leishmaniasis (VL) is life-threatening parasitic disease which is responsible for the death of 50,000 patients/year. Sodiumstibogluconate/paromomycin combined drugs are recommended to treat VL in East Africa. However, the adverse effect of those drugs is not studied in the study area. Therefore, the aim of the study was to assess serum amylase, lipase and associated factors among patients with these VL drugs. Cross-sectional study was conducted at the Universty of Gondar Comprehensive Specialized Hospital Kala-azar Research and Treatment Center from February-September 2020 G.C. Descriptive data was presented by tables, charts and graphs. Data was entered by EpiData 3.1 then exported to STATA 14.1 SE, for analysis, paired t-test was used, for factors correlation and multivariate regression was used. The mean ± SD level of serum amylase and lipase at TOC showed a statistically significant elevation (P<0.001) as compared to its level before treatment. As conclusion, there was an increase in mean serum amylase and lipase after a patient taking the drugs. Therfore, the elevated result of these biochemical profiles was mainly associated with drug induced adverse effects.