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Zero-noise extrapolation (ZNE) is a widely used quantum error mitigation technique that artificially amplifies circuit noise and then extrapolates the results to the noise-free circuit. A common ZNE approach is Richardson extrapolation, which relies on polynomial interpolation. Despite its simplicity, efficient implementations of Richardson extrapolation face several challenges, including approximation errors from the non-polynomial behavior of noise channels, overfitting due to polynomial interpolation, and exponentially amplified measurement noise. This paper provides a comprehensive analysis of these challenges, presenting bias and variance bounds that quantify approximation errors. Additionally, for any precision $\epsilon$, our results offer an estimate of the necessary sample complexity. We further extend the analysis to polynomial least squares-based extrapolation, which mitigates measurement noise and avoids overfitting. Finally, we propose a strategy for simultaneously mitigating circuit and algorithmic errors in the Trotter-Suzuki algorithm by jointly scaling the time step size and the noise level. This strategy provides a practical tool to enhance the reliability of near-term quantum computations. We support our theoretical findings with numerical experiments.