As one of the commonly isolated endophytic fungi, Alternaria has been known for the production of numerous secondary metabolites (SMs). However, its detailed genomic features and SM biosynthetic potential have not been extensively studied thus far. The present work focuses on the whole-genome sequencing and assembly of an endophytic strain Alternaria sp. SPS-2 derived from Echrysantha chrysantha Lindl. and gene annotation using various bioinformatic tools. The results of this study suggested that the genome of strain SPS-2 was 33.4 Mb in size with a GC content of 51% and an N50 scaffold of 2.6 Mb, and 9789 protein-coding genes, including 644 CAZyme-encoding genes, were discovered in strain SPS-2 through KEGG enrichment analysis. The antiSMASH results indicated that strain SPS-2 harbored 22 SM biosynthetic gene clusters (BGCs), 14 of which are cryptic and unknown. LS–MS/MS and GNPS-based analyses suggested that this endophytic fungus is a potential producer of bioactive SMs and merits further exploration and development.