Desert rose (Adenium obesum) is a succulent plant that is native to the Arabian Peninsula. It has great commercial value with exuberant structure and flowering. It can be propagated by seeds to ensure maximum development of the caudex. Despite its high economic value, studies on its propagation are still required. The aim of this study was to evaluate seed germination performance and seedling development of desert rose seedlings in different substrates. Treatments comprised five different substrate compositions: S1 (Soil), S2 (Sand), S3 (Carolina Soil commercial substrate), S4 (Sand + Carolina Soil), and S5 (Soil+ Carolina Soil). The following were evaluated using uni- and multi-variate approaches: germination, first count, germination speed index, caudex diameter, number of leaves, seedling length, root length, shoot length, and fresh mass and dry mass. Sand is the ideal substrate for the germination of A. obesum seeds, while for forming seedlings, mixtures of the Carolina Soil commercial substrate with sand or soil should be used.