The mechanical and physical properties of timber structures could be affected by a combination of loading, moisture content, temperature, biological activity, etc. This paper focuses on the optimal design of new timber structures subjected to fungal decay. Among the optimization methods available in the literature, this study considers a Time-Dependent Reliability Based-Design Optimization (TD-RBDO) approach. The TD-RBDO aims at ensuring a target reliability level during the operational life by considering deterioration and the uncertainties related inherent to materials properties, models and climate. This approach is applied to design optimization of a timber truss subjected to an aggressive (very humid) French climate. The performance of the optimized solution is compared, in terms of safety, with solutions estimated from Deterministic Design Optimization (DDO) and Reliability-Based Design Optimization (RBDO) approaches. The overall results indicate that the optimized solution of TD-RBDO reduces ensures a target reliability level during the whole structural lifetime.