Aim: To determine if Fourier-transform infrared spectroscopy (FTIR) could distinguish chronic periodontitis (CP) and aggressive periodontitis (AgP) patients by cross-sectional salivary spectral analyses and to assess the potential confounding influence of smoking on discriminating spectral signatures. Methods: FTIR analysis of saliva collected from patients with CP (n = 18, 7 smokers), AgP (n = 23, 9 smokers) was performed. Smoking status was confirmed by salivary cotinine analysis. Spectral band area analysis, hierarchical cluster analysis was performed. Results: Spectral analyses indicated significantly lower lipid, phospholipid, protein, amino acid, lactic acid, nucleic acid contents in smoker than non-smoker AgP group. Amino acid, phospholipid, lactic acid contents were significantly lower in smoker than non-smoker CP group. Thiocyanate levels successfully differentiated smokers from non-smokers, irrespective of periodontal status. Cluster analysis to discriminate smokers from non-smokers and CP from AgP was highly promising. Conclusions: FTIR can be employed to discriminate smokers from non-smokers and CP from AgP.