Large-scale pre-trained models have achieved remarkable success in a variety of scenarios and applications, but how to leverage them to improve the prediction reliability of downstream models is undesirably under-explored. Moreover, modern neural networks have been found to be poorly calibrated and make overconfident predictions regardless of inherent sample difficulty and data uncertainty. To address this issue, we propose to utilize large-scale pre-trained models to guide downstream model training with sample difficulty-aware entropy regularization. Pre-trained models that have been exposed to large-scale datasets and do not overfit the downstream training classes enable us to measure each training sample difficulty via feature-space Gaussian modeling and relative Mahalanobis distance computation. Importantly, by adaptively penalizing overconfident prediction based on the sample's difficulty, we simultaneously improve accuracy and uncertainty calibration on various challenging benchmarks, consistently surpassing competitive baselines for reliable prediction.