Detector and column saturations are problematic in comprehensive two-dimensional gas chromatography (GC×GC) data analysis. This limits the application of GC×GC in metabolomics research. To address the problems caused by detector and column saturations, we propose a two-stage data processing strategy that will incorporate a targeted data processing and cleaning approach upstream of the "standard" untargeted analysis. By using the retention time and mass spectrometry (MS) data stored in a library, the annotation and quantification of the targeted saturated peaks have been significantly improved. After subtracting the nonperfected signals caused by saturation, peaks of coelutes can be annotated more accurately. Our research shows that the target-guided method has broad application prospects in the data analysis of GC×GC chromatograms of complex samples.