Drug-Target Interaction (DTI) prediction is a key task in drug discovery and repurposing. The challenge lies in how to integrate multi-source heterogeneous features to characterize the complex relationships between drugs and targets comprehensively. To address the shortcomings of traditional methods that rely on a single data source and model complex nonlinear relationships in a low-quality way, a DTI prediction method based on Structure-Network collaborative features and grid-attention enhanced KAN (Kolmogorov-Arnold Network) (SNKDTI) was proposed. Firstly, a feature extraction strategy based on structure and network collaboration was designed: for drug representation, molecular fingerprints were fused with graph embedding methods to quantify chemical structures; for target representation, traditional physicochemical encoding was combined with pre-trained models to extract sequence features. Meanwhile, heterogeneous networks such as drug-disease associations and protein-protein interactions were introduced, network topological features were extracted by using the Random Walk with Restart (RWR) algorithm, and the features were compressed by using a Denoising AutoEncoder (DAE), so as to integrate structural and network information of drugs and targets. Secondly, a Heterogeneous Biological Information Network (HBIN) was constructed to carry out feature propagation by using a Graph Convolutional Network (GCN). Additionally, a Grid-Attention enhanced KAN (GA-KAN) was proposed, which introduced multiple learnable B-spline basis function grids and attention mechanisms to achieve adaptive combinations of multiple nonlinear mapping modules, thereby enhancing the model’s expressive power and input adaptability. Finally, a Gradient Boosting Decision Tree (GBDT) was used to build an end-to-end prediction framework. Experimental results of comparing the proposed method and benchmark methods on public datasets show that SNKDTI achieves improvements of 0.81%, 1.36%, and 3.29% in Area Under the receiver operating characteristic Curve (AUC), Area Under the Precision-Recall curve (AUPR), and F1-score, respectively, over the best-performing benchmark methods. The above prove that SNKDTI enhances accuracy, robustness, and generalization ability significantly, providing an efficient tool for new drug target screening.