Pedilanthus tithymaloids is a popular temperate indoor succulent ornamental plant and is highly marketable. However, the appropriate propagation techniques should be adopted to solve the rooting issues of cuttings. Therefore, the present research was designed to specify the optimal indole−3−butyric acid (IBA) concentration and rooting medium type for obtaining good rooting and healthy plants. Three IBA levels (0, 1.0, 2.0, and 3.0 g L−1 ) and five growing mediums (sand, sand: clay, sand: peat moss, sand: perlite, and sand: vermiculite as 1:1, v/v) were used. The experiment was performed in a randomized complete block design in three replications. The obtained data illustrated that roots number per cutting and rooting percentage reached the maximum values by treating P. tithymaloids cuttings with 3.0 g L−1 IBA x sand: perlite or sand: vermiculite medium. Cultivating the treated-IBA 3.0 g L−1 cuttings of P. tithymaloids in sand: perlite showed the most enhancements in plant height, branches number and leaves number, leaf area and herb dry weight. However, the heaviest root dry weight was noticed with IBA 3.0 g L−1 x sand: peat moss medium. Except sand medium, all other tested media in combination with IBA at 1.0, 2.0–3.0 g L−1 showed remarkable stimulation effect on chlorophyll content. Sand: vermiculite mixture x IBA at 2.0 g L−1 was the effective practice for improving carbohydrates percentage. By studying the anatomical changes of the adventitious root of P. tithymaloids plant, it was found that there was an increase in the root diameter, phloem and xylem tissues and xylem vessels diameter due to growing in sand: perlite x 3.0 g L−1 IBA. In conclusion, dipping the cuttings bases of P. tithymaloids in 3.0 g L−1 IBA and cultivation in sand: perlite considered the most effective combination practice for better rooting ability and growth and could be advisable for commercial production