Cissus rotundifolia is a climbing native to the Arabian Peninsula down the Eastern side of Africa to Limpopo and Mpumalanga and KwaZulu-Natal in South Africa. It grows in dry woodland and bush, from 400–1,700 m above sea level. The extent of occurrence (EOO) estimated at 6,394,683 km² exceeds the limits Endangered categories and the area of occupancy (AOO) estimated at 740 km² falls within the limits of the Vulnerable category under subcriterion B2. This species is known from 229 herbarium specimens collected between 1894 and 2017 and can be considered as common. Many collecting sites are located in protected areas like Virunga National Park (Democratic Republic of the Congo), Rusizi National Park (Burundi), Kibwezi Forest Reserve (Kenya), Awash National Park, Omo National Park (Ethiopia), Posto Agrário do Mazeminhama Reserva Ecológica (Mozambique), Lake Manyara National Park, Minziro Forest Reserve, Mombo Forest Reserve, Selous Game Reserve (Tanzania), False Bay Park, Kruger National Park, Mkuze Game Reserve (South Africa), Balcad Nature Reserve (Somalia). The other ones lie outside protected areas where its habitat is subject to increasing human activities, like bushfires, cutting of firewood, crop cultivation, etc. The species has been introduced to several countries like Australia, India, Hawaii, Mauritius, and the Seychelles (Bosser et al. 1997, Staples et al. 2000, Acevedo-Rodríguez and Strong 2012, Evenhuis and Eldredge 2012, HPWRA 2006, Senterre et al. 2017) where it is invasive and is considered as a weed. Considering its threats, the number of locations exceeds 30 and any information leads us to infer a continuing decline. Based on the information above, C. rotundifolia is listed as Least Concern.

Cissus rotundifolia is a climbing native to the Arabian Peninsula down the Eastern side of Africa to Limpopo and Mpumalanga, South Africa, and has been introduced to Australia, India, Hawaii, Mauritius, and the Seychelles. The species is native to the following countries: Burundi, Eritrea, Ethiopia, Somalia, Sudan [s.], Kenya, Tanzania, Uganda, Democratic Republic of the Congo, Eswatini, Malawi, Mozambique, Zambia, Zimbabwe, South Africa (KwaZulu-Natal, Transvaal), Swaziland, Saudi Arabia [s.w.], Yemen (Dewit and Willems 1960, Wild and Drummond 1966, Reekmans 1980, Audru et al. 1994, Darbyshire et al. 2015). It grows between 400–1,700 m asl.

Cissus rotundifolia is known from 229 herbarium specimens collected between 1859 and 2017 which represent 15 subpopulations and more than 30 locations.

The species is a perennial, evergreen climber (Wild and Drummond 1966). It is found in dry woodland and bush.

Expanding settlements and agriculture are a threat to this species, however overall, it is expanding its range.

Cissus rotundifolia has been used in traditional medicine to treat burns, skin diseases, liver and gastrointestinal disorders (Jawaher et al. 2020) recorded uses for this species.

This species is found in Virunga National Park (Democratic Republic of the Congo), Rusizi National Park (Burundi), Kibwezi Forest Reserve (Kenya), Awash National Park, Omo National Park (Ethiopia), Posto Agrário do Mazeminhama Reserva Ecológica (Mozambique), Lake Manyara National Park, Minziro Forest Reserve, Mombo Forest Reserve, Selous Game Reserve (Tanzania), False Bay Park, Kruger National Park, Mkuze Game Reserve (South Africa), Balcad Nature Reserve (Somalia). The species is in at least 10 ex situ collections (BGCI 2023).