Coronavirus disease-2019 (COVID-19) has shattered the public health delivery system of most of the countries of the world. COVID-19 displays variable clinical presentations. The severe COVID-19 represents a fulminant pathological condition and most of the patients run a downhill course if extensive medical measures are not adopted. The major challenges about COVID-19 are related to develop strategies to manage huge populations of mild and moderate cases of COVID-19 with two realistic purposes: (1) early negativity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and (2) arrest of progression of moderate COVID-19 patients from developing severe complications. Although several medications have been repurposed for these purposes, none of these have passed the test of time in global perspective. Thus, there remains a pressing need to develop new and novel innovative management strategies for these patients as new variants of SARS-CoV-2 have been destroying the normal public health delivery system of different countries from time to time. The study presented here has checked the safety and efficacy of a herbal medication, leaves of Euphorbia neriifolia Linn (E. neriifolia), in mild and moderate COVID-19 patients. Sixty patients (30 mild COVID-19 and 30 moderate COVID-19) were enrolled in the study. Fifteen mild COVID-19 patients received standard of care (SOC) management, and the remaining 15 patients received SOC plus E. neriifolia. The moderate COVID-19 patients similarly received either SOC (N = 15) or SOC plus E. neriifolia (N = 15). Although there were marked diversity regarding biochemical parameters of these patients at entry, the moderate COVID-19 patients receiving E. neriifolia showed decrease in C-reactive protein and D-dimer and increase in oxygen saturation 7 days after trial commencement. However, these improvements were not detected in moderate COVID-19 patients receiving SOC. Hospital staying was significantly lower in both mild and moderate COVID-19 patients receiving SOC plus E. neriifolia than those receiving only SOC. Taken together, it may be proposed that usage of E. neriifolia may have beneficial effects regarding management for COVID-19 patients, especially for those in developing and resource-constrained countries, although a conclusive statement may not be given due to small sample size. This herbal medication is also pertinent in the context of emergence of OMICRON variant of COVID-19 as the overload of SARS-CoV-2-infecetd patients may be addressed considerably by this medication without hospitalization, if proper communication between patients and physicians can be ensured.