The antidepressants trazodone and nefazodone were approved some four and three decades ago, respectively. Their action is thought to be mediated - at least in part - by inhibition of the serotonin transporter (SERT/SLC6A4). Surprisingly, their mode of action on SERT has not been characterized. Here we show that - similar to the chemically related drug vilazodone - trazodone and nefazodone are allosteric ligands, which inhibit uptake by and transport-associated currents through SERT in a mixed-competitive and non-competitive manner, respectively. Contrary to noribogaine and its congeners, all three compounds preferentially interact with the Na+-bound outward-facing state of SERT. Nevertheless, they act as pharmacochaperones and rescue the folding-deficient variant SERT-P601A/G602A. The vast majority of disease-associated point mutations of SLC6 (solute carrier-6) family members impair folding of the encoded transporter proteins. Our findings indicate that their folding defect can be remedied by targeting allosteric sites on SLC6 transporters. Significance Statement The serotonin transporter is a member of the solute carrier 6 family and is the target of numerous antidepressants. Trazodone and nefazodone have long been used as antidepressants. Here we show that their inhibition of the serotonin transporter digressed from the competiti-ve mode seen with other antidepressants. Trazodone and nefazodone rescued a folding-deficient variant of the serotonin transporter. This finding demonstrates that folding defects of mutated solute carrier-6 family members can also be corrected by allosteric ligands.