Background: Graphene quantum dots (GQDs) have great potential for bioimaging, biosensor, drug carrier, theranostics, and are recently reported as therapeutic agents to treat amylosis and inflammation. Most types of GQDs have proven low toxicity in previous studies, but data about the transcriptomic responses of in vivo systems exposed to various GQDs remains largely unknown. Results: We examined the mRNA and microRNA (miRNA) expression changes of zebrafish embryos exposed to four types of GQDs at a safe concentration (100 µg/mL), respectively as raw graphene quantum dots (R-GQDs), graphene oxide quantum dots (GOQDs), carboxyl GQDs (C-GQDs), and aminated GQDs (A-GQDs). The four GQDs elicited the number of differentially expressed genes (DEGs) in a decreasing order of A-GQDs, GOQDs, C-GQDs and R-GQDs to act on protein folding, potassium (K+) and calcium (Ca2+) channels, and spliceosome to varying degrees. Among the four GQDs, A-GQDs caused more genotoxic effects associated with lipid and hormone metabolism, MAPK signaling pathway, complement system, and ferropotosis. miRNA-seq data revealed that GOQDs aroused more differentially expressed miRNAs (DEMs), far exceed the total number of DEMs induced by the other three GQDs. dre-miR-735-5p and its potentially interactive gene-myogenin (myog) were identified as the only negatively-correlated miRNA-target gene pair shared by the four GQDs treatments. Conclusion: Taken together, this study provided substantial data underlying the common and specific transcriptomic responses of in vivo systems exposed to various types of GQDs, and also indicated the potential medicinal values of GQDs for ion antagonists and spliceosome-targeted therapies.