Background The presence of undesirable substances, including pesticides (xenobiotics) in betel leaf (Piper betel), is a great concern for consumers as it is chewed and consumed directly. To protect the consumer’s health, a modified QuEChERS method for monitoring purposes and subsequent decontamination process have been developed. Objective The goal of this work was to establish a multi-residue analytical method for monitoring non-permitted organophosphorus pesticide residues in betel leaf, as well as cost-effective cleaning strategies. Methods The homogenized 15 g samples (20 betel leaf samples collected in West Bengal, India) were extracted with modified QuEChERS method using acetonitrile, reconstituted to acetone, and finally analyzed by GC-MS/MS. Possible decontamination techniques (like tap water washing, 2% saltwater washing and luke-warm water washing) were evaluated. Results The limit of detection ranged from 0.003 to 0.005 mg/kg and limit of quantification was 0.01 mg/kg. Recoveries ranged from 80% to 120% with RSDr 9%. One sample was found to contain three pesticides 4 to 7 times higher than MRLs. Suggested decontamination methods allowed reducing toxic traces below European limits. Conclusions The suggested approach is useful for determining pesticide residues in betel leaves quickly. Traditional techniques of processing betel leaves may reduce pesticide residues below regulatory limits. Highlights A multi-residue method and decontamination of pesticides in betel leaf utilizing QuEChERS-GC-MS/MS technology with satisfactory method performance was achieved. Domestic decontamination techniques have a high efficacy in reducing pesticide residues from betel leaves making them safe for human consumption.