Aims: Brain diseases refer to intracranial tissue and organ inflammation, vascular diseases, tumors, degeneration, malformations, genetic diseases, immune diseases, nutritional and metabolic diseases, poisoning, trauma, parasitic diseases, etc. Taking Alzheimer’s disease (AD) as an example, the number of patients dramatically increases in developed countries. By 2025, the number of elderly patients with AD aged 65 and over will reach 7.1 million, an increase of nearly 29% over the 5.5 million patients of the same age in 2018. Unless medical breakthroughs are made, AD patients may increase from 5.5 million to 13.8 million by 2050, almost three times the original. Researchers have focused on developing complex machine learning (ML) algorithms, i.e., convolutional neural networks (CNNs), containing millions of parameters. However, CNN models need many training samples. A small number of training samples in CNN models may lead to overfitting problems. With the continuous research of CNN, other networks have been proposed, such as randomized neural networks (RNNs). Schmidt neural network (SNN), random vector functional link (RVFL), and extreme learning machine (ELM) are three types of RNNs.Methods: We propose three novel models to classify brain diseases to cope with these problems. The proposed models are DenseNet-based SNN (DSNN), DenseNet-based RVFL (DRVFL), and DenseNet-based ELM (DELM). The backbone of the three proposed models is the pre-trained “customize” DenseNet. The modified DenseNet is fine-tuned on the empirical dataset. Finally, the last five layers of the fine-tuned DenseNet are substituted by SNN, ELM, and RVFL, respectively.Results: Overall, the DSNN gets the best performance among the three proposed models in classification performance. We evaluate the proposed DSNN by five-fold cross-validation. The accuracy, sensitivity, specificity, precision, and F1-score of the proposed DSNN on the test set are 98.46% ± 2.05%, 100.00% ± 0.00%, 85.00% ± 20.00%, 98.36% ± 2.17%, and 99.16% ± 1.11%, respectively. The proposed DSNN is compared with restricted DenseNet, spiking neural network, and other state-of-the-art methods. Finally, our model obtains the best results among all models.Conclusions: DSNN is an effective model for classifying brain diseases.