Dithiocarbamates (DTC) are one of the main classes of fungicides and have been used for the control of fungal diseases on a large variety of crops. In this work, a fast and cheap sample preparation procedure for DTC analysis in yerba mate using GC-MS is described. For this, a multivariate approach by Placket–Burmann Design (PBD) have been carried out to screen the parameters that may affect DTC extraction, followed by a Central Composite Design (CCD) involved in the optimization of significant ones. Sample amount, HCl concentration and volume, SnCl2 concentration and volume, isooctane volume, and extraction time and temperature were evaluated in miniaturization step. A complete validation study was performed (linearity, matrix effect, limit of detection and quantification, accuracy, repeatability and intermediate precision). Blank yerba mate samples were spiked with thiram at 0.1, 0.5 and 2 mg CS2 kg–1 (n = 7) by two analysts. The method was validated according to SANTE guideline and presented satisfactory accuracy and precision (94.5–110.8% and RSD ≤ 8%). The analytical curves were linear in the concentration range of 0.05–10 mg CS2 L−1 (r2 > 0.999), and the matrix effect was not significant (-14.9%). LODm and LOQm were 0.05 and 0.1 mg CS2 kg−1, respectively. The screening experiment obtained by the use of PBD indicates that three factors were significant; concentration and volume of hydrolysis acid solution containing SnCl2 1.5%, and time of hydrolysis were further optimized. The optimized and validated method presented important advantages: 5x reduction of the isooctane volume used in DTC extraction; increase from 1 to 30 sample extractions using the same volume of extraction solution and without HCl; 200% increase in extraction speed; smaller amount of processed sample; and less waste volume aiming to green chemistry principles. The significance of multivariate approach evidenced to be influential in improving the extraction efficiency.