Green monkey orange (Strychnos spinosa) is an important multipurpose tree in rural communities in sub-Saharan Africa, including Benin. The objectives of this study were to (i) examine the various indigenous uses of Strychnos spinosa, (ii) assess local perception of the major threats to Strychnos spinosa, and (iii) identify the conservation strategies adopted by local communities to ensure its sustainable use in Benin. A participatory rural appraisal study was undertaken across three climatic zones in Benin. Data were collected through structured questionnaires involving 733 informants from 22 ethnic and 7 sociolinguistic groups. Correspondence analysis (CA) showed that S. spinosa is most widely used in the Sudanian zone (20 uses). About 73% of the informants used Strychnos spinosa as food, and 68% used it for medicine. The most valued organs were fruits, leaves, bark, and seeds. The major threats to Strychnos spinosa were human activities rather than climatic factors. Religion and cultural values were the main strategies adopted by local communities to conserve the species. The value of Strychnos spinosa is well appreciated in Benin, and local knowledge depends on the particular climatic zone, ethnic group, study level, and gender.