Sisal—Agave sisalana Perrine ex. Engelm—is a key economical and social crop in the semi-arid region of Brazil, especially in the Bahia state. Sisal is severely affected by Aspergillus niger Thieg, the causal agent of sisal red rot. Currently, existing control strategies are fruitless. Here, we tested different homeopathic drugs Carbo vegetabilis, Ferrum metallicum, Natrum muriaticum, phosphorus and sulphur at centesimal Hahnemannian (CH) dynamizations, of 3CH, 5CH, 7CH, 9CH and 12CH, on Aspergillus niger. We measured in vitro growth inhibition, sporulation and germination of Aspergillus niger during 12 days. We assessed in planta Aspergillus niger incidence and disease severity. Our results show that homeopathic drugs inhibited Aspergillus niger growth in vitro, in a dynamization-dependent way. Natrum muriaticum 5CH revealed the higher inhibition of 66 %, whereas sulphur 5CH yielded the lowest inhibition of 6.4 %. Spore production was stimulated using all homeopathic drugs at all dynamization levels, whereas spore germination was reduced. In planta assays revealed different results from in vitro assays, corroborating that in planta and in vitro effectiveness is different according to the homeopathic drugs applied. Here, disease incidence was not reduced significantly, but disease severity was lower in treated plants, of 27.8 % using Ferrum metallicum 9CH than in control trials, of 73.6 %. Overall, our findings suggest that homeopathic drugs could be a good strategy to control Aspergillus niger incidence in sisal plants.