Drug-Induced Liver Injury (DILI) is a grave global adverse event that can result in fatal consequences, causing drug failures, market withdrawals, and regulatory warnings, leading to substantial financial losses. The early detection of DILI remains a significant challenge in global healthcare. Although circulating microRNAs (miRs) show promise as clinical biomarkers for DILI, the current analytical methods for their measurement are insufficient. There is a pressing need for rapid and reliable miR detection methods that eliminate the need for nucleic acid extraction and PCR-based amplification. This review highlights recent advancements achieved by integrating Dynamic Chemical Labelling (DCL) with Luminex xMAP technology. This powerful combination has resulted in groundbreaking bead-based assays that allow (1) the direct, multiplex detection of miRs, and (2) the simultaneous testing of miR and protein biomarkers. This triple capability enables a comprehensive assessment that significantly enhances the detection and analysis of crucial biomarkers, thus improving the understanding and diagnosis of DILI. In conclusion, this review offers valuable insights into the capabilities and potential applications of these groundbreaking assays in DILI research, as well as their potential use in other diagnostic and research domains that require direct or multiplex analysis of miRs or analysis of miRs in combination with proteins.