Introduction and objective: The “honeymoon” (HM) phase, which lasts an average of 7-9 months and very infrequently longer, is a brief recovery in pancreatic β-cell activity that occurs in about 50% of individuals with newly diagnosed Type 1 Diabetes (T1D). Although the causes for it to occur are yet unknown, this phase offers an important window for therapies aimed at maintaining insulin secretion. Here we comprehensively profiled for the first time children with new-onset T1D in an extended honeymoon phase (ExMoon), thus revealing potential molecular targets for maintaining β-cell bulk and function. Methods: Insulin dose-adjusted HbA1c (IDAA1c) <9 and C peptide >300 pmol/l maintained for a minimum of 9 months were the criteria used to select patients in ExMoon (n=10). The signature of age and gender-matched T1D patients who were not in the HM phase were compared to that of ExMoon patients, while 10 matched non-diabetic patients were included as supplementary controls. By using flow cytometry, ELISpot, multiplexed immunoassay, mass spectrometry, and RNA sequencing, we investigated the immunophenotype, immunoreactivity to islet antigens, serum secretome, proteome/metabolome/lipidome, and PBMC transcriptome, respectively. Results: Differential serum levels of immune factors (IP-10, IL-2, FGF2), proteins (TGM2, SIR4), metabolites (kynurenine), and lipids (myristic acid and monoarachidonic acid triglyceride 18:0_38:6) were observed in ExMoon compared to the T1D group. PBMCs obtained from patients of the two groups exhibited distinct expression patterns of ERAP2, TSKS mRNAs, and of miR-339-3p, miR-8087-3p miRNAs. No differences were found in the proportion of immune cell subpopulations and islet autoreactivity between the ExMoon and T1D patient cohorts. Conclusion: Our unbiased multiomic approach identified several immune and non-immune factors as potential molecular candidates for targeted therapies aimed at preserving β-cell mass and function.