Anthelmintic treatment is the most common way of controlling nematode infections in ruminants even though several countries have reported anthelmintic resistance (AR), resulting in limitation for sustainable small ruminant production. The aim of the present study was to evaluate the knowledge of resource-poor sheep farmers in Limpopo province of South Africa on the use of anthelmintics. A questionnaire regarding helminthosis control practices was administered to small ruminant farmers in five districts of Limpopo province namely Capricorn, Sekhukhune, Waterberg, Vhembe, and Mopani. A total of 77 resource-poor farmers were interviewed between June and August of 2017 using a structured questionnaire with a combination of qualitative and quantitative open-ended questions. The interviewed farmers were divided into three groups based on their farming experience (< 5; 6–10, and ˃ 10 years of farming experience). Limited farming experience was shown as one of the risks, as farmers that owned sheep for less than 10 years could not identify the symptoms of gastrointestinal parasites infection and did not know how nematodes are transmitted to animals. However, no significant difference (p < 0.05) was found to exist between the three groups of farmers in terms of clinical signs identification and correct application of anthelmintics. About 43% of the respondents were unaware of gastrointestinal nematodes (GI) that infect sheep, could not identify the clinical symptoms of gastrointestinal nematodes infection, and only 34% knew how animals become infected. Although 67.5% of farmers mentioned that they never dose their sheep, 32.5% use anthelmintics at varying times in a year. None of the farmers weighed their sheep before dosing them instead visual appraisal of individual weight was the most common means of estimating the anthelmintic dose. The above information is an indication of risks associated with possible occurrence of anthelmintic resistance in the study areas. There is therefore, a need to give training to resource-poor farmers of small stock on proper application of anthelmintic treatment and to educate them on how to prevent development of AR. Future studies on AR should also be conducted in the province in flocks with high-treatment frequencies to establish the occurrence of AR using both in vivo and in vitro methods. The most common risk factor associated with the occurrence of AR in all the five districts of Limpopo province was found to be the use of anthelmintics without weighing the animals to determine the correct dosage.