Urolithiasis is a public health problem with limited treatment options. In the Ethiopian folk medicine, there is a claim that medicinal plants can treat urolithiasis. The present study investigated the safety, antioxidant activities and antiurolithiatic efficacies of Achyrathes aspera, Rumex abyssinicus, Satureja punctata, Chenopodium murale, Aloe pulcherrima, Chenopodium ambrosioides, Inula confertiflora, Gomphocarpus fruticosus and Commiphora myrrha extracts. Primarily, thirteen years retrospective clinical records from St. Paul's Tertiary Referral Hospital were retrieved and analyzed to estimate the overall prevalence of urolithiasis in Ethiopia. In addition, plant extracts were tested for acute and sub-acute toxicity in female Wistar rats. The in vitro DPPH (2,2-diphenyl-1-picrylhydrazyl) and calcium oxalate (CaOx) assays were measured using UV-Vis-NIR spectrophotometery. Also, urolithiasis was induced in male Wistar rats by feeding ethylene glycolated (0.75%) water for 28 days. Preventive and curative studies were based on oral exposure of rats to 200 mg/kg extracts for 14 and 28 days, respectively. Urine samples were collected on 13th and 27th day before sacrificing the rats, whereas the liver and kidneys collected after sacrificing on days 14 and 28. Blood samples were collected from retro-orbital sinus under the anaesthetic condition. The bioactive constituents of G. fruticosus extracts were characterized by GC-MS analysis. Among 32,370 surgically treated patients, referred from all over the country, 2.3% (757) urolithiatic cases were recorded. Trend analysis revealed an increasing prevalence of urinary stones. Acute toxicity tests resulted in body weight loss for C. murale, R. abyssinicus, C. ambrosioides and I. confertiflora extracts at dose 2000 mg/kg. Moreover, C. murale (p