Inflammation is a complex, natural protective response towards different stimuli characterized by the dilation and permeation of the blood vessels with a surge in leukocytes in the tissues. The current treatment involves the use of anti-inflammatory drugs, corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs), which have been associated with adverse side effects especially gastrointestinal ulcers. Therefore, there is a growing need to explore alternative sources from medicinal plants. In the present study we investigated anti-inflammatory activities of the leaves of the Kenyan stinging nettle using in vivo and in silico molecular docking. Molecular identification of plant sample was carried out based on DNA barcoding. Crude extracts were prepared using water and methanol: dichloromethane (1:1) and preliminary identification of total phenolic and flavonoids was carried out using Folin-Ciocalteu and aluminum chloride colorimetric methods, respectively. The classical model of Carrageenan- induced paw edema was used to test the in vivo anti-inflammatory activity of the extracts. The extract was screened using Laser Raman Spectroscopy and Liquid Chromatography Mass Spectroscopy (LC-MS) and the molecular interaction between the identified compounds within the binding site of Cyclooxygenase-2 (COX-2) performed through molecular docking as the confirmatory tool of in vivo experiments. Based on DNA barcoding analysis, the plant sample was identified as Urtica species. The total phenolic content of the aqueous and methanol: dichloromethane extracts were 3.75 mg gallic acid equivalents (GAE)/g dry sample and 6.26 mg GAE/g dry sample while total flavonoid content were 0.3872 mg quercetin/g dry sample and 1.76 mg quercetin/g dry sample, respectively. The aqueous extract significantly (p < 0.05) reduced the paw edema in the Carrageenan model of inflammation. LC-MS confirmed the presence of 19 phytochemicals, of which 10 and 9 were phenolic and flavonoid compounds, respectively. From these identified compounds quercetin attained the lowest binding energy when complexed with COX-2, followed by rhamnetin, quercetin rhamnoside, epigallocatechin gallate and chlorogenic acid. Molecular docking studies supported the in vivo findings and confirmed the anti-inflammatory potential of Urtica sp. These findings suggest Urtica sp. is a potential source of bioactive compounds that could be employed in the future development of anti-inflammation drugs. Further studies can attempt to assess the individual isolated active compound(s) for their anti-inflammatory activity.