This work explores the bioanalytical methods and green procedures for the synthesis of small molecules–ionic liquids with N-glycans (GLc-O-SMol-HmILs), good applicable materials with bioactive properties as potential drugs anti-SARS-CoV-2. Methylimidazolium N-ethylamine has good applicability and is an active ionic liquid that acts with oligosaccharides very easily. Particularly, this ionic liquid is employed in the modification of oligosacharides obtained from human milk, lactoferrin (Hm), to produce a novel small molecule (Gl-SM-o-IL-HmLf). The advanced analytical techniques of UPLC/ESI-QTOF and MALDI-TOF mass spectrometry illustrated the identification and investigation of the modified small molecules–glycoproteins–ionic liquids (Glc-SM-IL-HmLf). Small molecules may be provided as significant potential drug candidates for inhibiting the selected targets of main protease (Mpro), RNA-dependent RNA polymerase (RdRp), Papain-like protease (PLpro) and trans-membrane protease serine 2 (TMPRSS2). The molecule had a slightly stronger interaction than remdesivir with Mpro and TMPRSS2. Similarly, the modified compound interacted with RdRp at a comparable level to the standard drug, which had slightly lower binding energy than remdesivir and its derivatives, and the novel small molecule-IL-HmLf has strong 10 H-bonding with the structures of four targets of main protease. The characterization and quantification of small molecules–ionic liquids linked to oligosaccharides were investigated by LCMS, GCMS, NMR, and UV-vis spectrometer. Molecular docking disclosed the bio-activity of modifying glycoprotein–small Glc-IL-HmLf-molecules by elucidating their interactions with the inspected targets.