Bursicon is a heterodimeric neuropeptide formed of bursicon α (burs α) and bursicon β (burs β) that controls cuticle tanning and wing expansion in insects. Burs α–α and burs β−β homodimers are also formed; they act via an unknown receptor to induce expression of prophylactic immune and stress genes during molting. Based on the hypothesis that burs β−β and/or bursicon influence expression of additional genes acting after the molt, we prepared and sequenced six Drosophila cDNA libraries from groups of flies separately injected with burs β−β, bursicon, or blank control. Compared to the control, the burs β−β treatments led to upregulation (by at least 1.5‐fold) of 262 genes at 0.5 h postinjection (PI) and 298 genes at 1 h PI; 323 genes at 0.5 h PI and 269 genes at 1h PI were downregulated (by at least 0.67). Similar changes were recorded following bursicon injections. Of these genes, expression of seven transcripts encoding cuticle proteins was upregulated and three downregulated by burs β−β; expression of nine transcripts encoding cuticle proteins were upregulated and four downregulated following bursicon treatments. Expression of dozens of genes involved in chitin metabolism was altered by the experimental treatments. We recorded parallel changes in expression of selected genes by transcriptome and qPCR analysis. These findings support our hypothesis that burs β−β and bursicon influence expression of additional genes acting after the molt. We report that burs β−β and bursicon act in cuticle synthesis and degradation by regulating the expression of cuticular protein and chitin metabolizing related genes.