To repair the blood–brain barrier (BBB) after traumatic brain injury (TBI) remains a multidisciplinary challenge. No first-line drugs are available. Here, we reported a novel and non-toxic functional negative-charged carbon dots (CDs) generated from green Semen pruni persicae and Carthamus tinctorius L. (TH-CDs) through a hydrothermal synthesis without any organic solvent. The surface of TH-CDs retained part functional groups of active pharmacophores from both drugs. TH-CDs could improve the neurological function, brain edema, neuronal damage, and the BBB permeability by tail vein injection of mice models without systemic toxicity. Furthermore, higher expression of tight junction proteins claudin 5 and ZO-1 was observed after TH-CDs administration, which may be due to the electrostatic interaction between TH-CDs and claudin 5. Our study highlights an inexpensive, green, non-toxic, and intravenous functional TH-CD, which represents a potential TBI treatment strategy.