Abstract Background Ulcerative colitis (UC) is characterized by confluent mucosal inflammation and erosions starting from the anal verge and extending to a variable extent, where patients often complain of diarrhea associated with rectal bleeding, abdominal tenderness, and weight loss. Numerous disease biomarkers have been studied in ulcerative colitis (UC) such as Erythrocyte sedimentation rate(ESR) and C- reactive protein(CRP). On the other hand, fecal calprotectin and Lactoferrin are more specific and sensitive but expensive and still not commonly used in clinical practice due to the need for on demand specimen collection. Objective To evaluate the role of the non-invasive biomarkers as an early predictor of mucosal healing in ulcerative colitis patients treated with biological therapy. Methods Twenty adult patients with ulcerative colitis who received biological therapy (after adequate screening) were included in our study. The patients met the indications for treatment with biological therapy according to European Crohn and Colitis Organization guidelines. The patients were presented to our IBD clinic at tropical medicine department, Ain shams university in the period from 1/2018 to 9/2021. Results There is a strong relationship between clinical response and mucosal healing at 6 months of starting biological therapy as 100% of patients who achieved mucosal healing showed clinical response. Median N/L ratio, median PLT/L ratio and CRP/albumin ratio were 1.58, 425 and 1.19 respectively in patients who achieved mucosal healing at 6 months after 3 months of starting biological therapy with statistical significance (p-value = 0.019, 0.019 and 0.008) respectively in comparison to the patients who didn’t achieve mucosal healing. Both median of L/M ratio and PLT/M ratio were decreased in patients achieved mucosal healing at 6 months after 3 months of starting biological therapy (3.43 and 660) respectively in comparison to patients who didn’t achieve mucosal healing but it didn’t reach any statistical significance. Conclusion Non invasive biomarkers at 3 months like N/L ratio, PLT/L ratio, L/M ratio and PLT/M ratio may be used as non invasive predictors of mucosal healing at 6 months after starting treatment with biological treatment.