Liquid crystal whispering-gallery-mode (WGM) sensing technology combines the high sensitivity of liquid crystal materials with the high precision characteristics of optical WGM, holding broad application prospects in substance detection, environmental monitoring, and biomedical fields. To enhance the accuracy and sensitivity of sensing measurements, accurate calibration of the WGM spectral lines is crucial. However, the irregular distribution of liquid crystal WGM spectra poses challenges to spectral calibration in practical applications. This paper proposes a method for calibrating irregular liquid crystal WGM spectra based on Savitzky-Golay filtering and Gaussian smoothing, advocating three principles of symmetry, high linearity, and rationality for spectral calibration. Spectral calibration is categorized into regular and irregular spectra. For regular spectra with good Lorentzian line shapes and Gaussian envelope profiles, the highest intensity spectral line, central wavelength, or spectral lines of adjacent modes with the same free spectral range can be selected as the resonance wavelength. For irregular spectra, three types are identified: (1) spectral missing peaks and intensity variations mainly caused by loss variations in resonance conditions; (2) spectral irregular splitting due to small defects or impurities in the liquid crystal microcavity, leading to asymmetric splitting of spectra; and (3) mixed-type variable spectra affected by complex measurement environments, resulting in various irregular changes. Through Savitzky-Golay filtering and Gaussian smoothing, spectral symmetry is effectively restored, and fitting linearity is improved, facilitating spectral calibration. To validate the effectiveness of the proposed method, experiments are designed for sensing different biological molecules using liquid crystal WGM mode, including trypsin (concentration range of 0.75～2.00 μg·mL^-1), pH (4.55～6.86), and DNA (concentration range of 90～490 μg·mL^-1). Experimental results demonstrate that using the proposed method and three principles for liquid crystal WGM mode spectral calibration and resonance peak selection, the linearity of sensing sensitivity exceeds 0.99, indicating good reliability and stability. This paper innovatively proposes an effective calibration method and three principles for irregular liquid crystal WGM mode spectral distribution, providing practical solutions and significant theoretical and methodological support for enhancing the accuracy and effectiveness of liquid crystal WGM mode sensing measurements, thereby holding important application and theoretical significance.