The proposed UniGuard is the first unified online detection framework capable of simultaneously addressing adversarial examples and backdoor attacks. UniGuard builds upon two key insights: first, both AE and backdoor attacks have to compromise the inference phase, making it possible to tackle them simultaneously during run-time via online detection. Second, an adversarial input, whether a perturbed sample in AE attacks or a trigger-carrying sample in backdoor attacks, exhibits distinctive trajectory signatures from a benign sample as it propagates through the layers of a DL model in forward inference. The propagation trajectory of the adversarial sample must deviate from that of its benign counterpart; otherwise, the adversarial objective cannot be fulfilled. Detecting these trajectory signatures is inherently challenging due to their subtlety; UniGuard overcomes this by treating the propagation trajectory as a time-series signal, leveraging LSTM and spectrum transformation to amplify differences between adversarial and benign trajectories that are subtle in the time domain. UniGuard exceptional efficiency and effectiveness have been extensively validated across various modalities (image, text, and audio) and tasks (classification and regression), ranging from diverse model architectures against a wide range of AE attacks and backdoor attacks, including challenging partial backdoors and dynamic triggers. When compared to SOTA methods, including ContraNet (NDSS 22) specific for AE detection and TED (IEEE SP 24) specific for backdoor detection, UniGuard consistently demonstrates superior performance, even when matched against each method's strengths in addressing their respective threats-each SOTA fails to parts of attack strategies while UniGuard succeeds for all.