<p><i>Aspilia africana</i> (Pers.) C. D. Adams is a widely used medicinal plant to traditionally treat many diseases in Africa, including diabetes mellitus, malaria, and cancer. Over the years, explosion of human population has led to increased use of <i>A. africana</i> for therapeutic and other purposes, remarkably decreasing its wild population and thereby necessitating cultivation. This study focused on developing an indirect somatic embryogenesis (ISE) method for <i>A. africana</i> from leaf explants. Effects of exogenous plant growth regulators (PGRs), adenosine 5-monophosphate (AMP), phytosulfokine-α (PSK), nicotinamide adenine dinucleotide (NAD), and silver nitrate (AgNO₃) on induction and development of somatic embryos were investigated. Induction of embryogenic callus and somatic embryogenesis were best achieved in Murashige and Skoog (MS) medium fortified with 0.1&#xa0;mg/L 2,4-Dichlorophenoxyacetic acid (2,4-D), 2.0&#xa0;mg/L benzylaminopurine (BAP), and 6.634 × 10⁻⁴ mg/L NAD at 91.67 ± 8.33% response and 8.00 ± 1.62 somatic embryos per explant. Differentiation and maturation of somatic embryos was optimally attained (2.33 ± 0.49 cotyledonary embryos per explant) in MS medium fortified with 0.5&#xa0;mg/L abscisic acid (ABA), 6.634 × 10⁻² mg/L NAD, 2.0&#xa0;mg/L AgNO₃, and 9&#xa0;g/L gelrite. Highest level of germination (35.71 ± 1.73%) and conversion to plantlets (24.00 ± 1.15%) were recorded in half strength MS medium augmented with 0.5&#xa0;mg/L gibberellic acid 3 (GA₃), 0.1&#xa0;mg/L naphthaleneacetic acid (NAA), and 2.0&#xa0;mg/L AgNO₃. Histological and flow cytometry analyses confirmed ISE and the genetic similarity of regenerants to zygotic embryo plants, respectively. This is the first report on ISE in <i>A. africana</i> and it would offer an alternative technique for rapid and sustainable seedling production, breeding improvement, and conservation of <i>A. africana.</i></p>