Background Lymphoedema is a pathological process that results from damage, infection, blockage, or genetic defects in the lymphatic system. The main causes of lower limb lymphoedema in Ethiopia are lymphatic filariasis (LF) and podoconiosis. Many natural products are being used for management of wound and inflammatory conditions in Ethiopia. Few of these products have been systematically evaluated using in vitro tests. Objective The objective of this study was to conduct in vitro cytotoxicity assays, anti-inflammatory, and wound healing activity tests on selected Ethiopian plant extracts. Methods The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate cytotoxicity of the plant extracts. For the anti-inflammatory activity, cyclooxygenase enzymes 1 (COX-1), cyclooxygenase enzymes 2 (COX-2) and 15-lipoxygenase enzyme inhibitory assay was used. Antioxidant activities were conducted using DPPH assay. Quantification of cell multiplication based on the measurement of BrdU incorporation during deoxyribonucleic acid (DNA) synthesis, was used to measure deoxyribonucleic acid (DNA) /cell proliferation. Results Azadirachta indica A. Juss (82%) and Lawosinia inermis L (87.6%) showed significant inhibition against COX-1 at 25 mg/ml, while Achyranthus aspera L (91.7%) and A. indica (95%) were effective in inhibiting COX-2 at the same concentration. Similarly, L. inermis L inhibited 88.8% of COX-2 at the same concentration. L. inermis (74.8%) showed the highest inhibitory activity against 15-LOX, followed by A. asper (73.1%) and A. indica (66%) at 25mg/ml. All the tested extracts showed free radical scavenging activity at 10 mg/ml. A. indica and L. inerms have shown better stimulation of human epidermal keratinocytes, with optimal stimulation observed between 2.5 mg/ml and 5 mg/ml of the extracts. Conclusion Plant extracts or compounds that inhibited these enzymatic inflammatory activities may contain potential drivers or templates for the development of effective anti-inflammatory drugs. Antioxidants that maintain non-toxic ROS levels in wound tissue can improve the wound healing process.