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The Ghanaian <i>Paenibacillus</i> sp. DE2SH (GenBank Accession Number: MH091697) is a prolific producer of potent antiparasitic alkaloids. Further detailed study of the culture broth of this strain produced the compound Paenidigyamycin G (<b>1</b>), which is a derivative of the known antiparasitic compound Paenidigyamycin A (<b>2</b>). Compound (<b>1</b>) was isolated on HPLC at t_R &#8776; 37.5 min and its structure determined by IR, UV, MS, 1D, and 2D-NMR data. Compound <b>1</b> produced weak to moderate antileishmanial and antitrypanosomal activity when tested against <i>Leishmania donovani</i> (Laveran and Mesnil) Ross (D10) and <i>Trypanosoma brucei</i> subsp. <i>brucei</i> strain GUTat 3.1 with IC₅₀ = 115.41 and 28.75 &#956;M, respectively. This result is interesting since the parent compound <b>2</b> is known to possess consistent and potent antiparasitic activity. However, <b>1</b> displayed a promising selectivity profile towards <i>T. brucei</i> subsp. <i>brucei</i> due to its relatively low toxicity against normal mouse macrophages RAW 264.7 cells (SI = 8.70). Given that compound <b>1</b> is also the main metabolite found in the hexane fraction of all extracts produced by <i>Paenibacillus</i> sp. DE2SH when it is co-cultured with other bacteria strains, it must possess some unique biological functions which should make it an excellent candidate for further biological activity screening in other bioassays.